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Neuromuscular disorders arise from pathologic abnormalities in muscle (myopathy), the nerve which innervates the muscle (neuropathy), or the junction between the two (neuromuscular junction disorders). The classification of these disorders is very broad encompassing a wide variety of underlying etiologies. The clinical history and physical examination are very important in narrowing the differential diagnosis. Ancillary testing provides an additional layer of granularity to assist in making the diagnosis. This may include a variety of laboratory tests, diagnostic muscle biopsy, electromyography (EMG), or nerve conduction studies. In order to understand muscle pathology, one must understand the organization of skeletal muscle and the histochemical stains performed to help distinguish between different diseases.

Organization of Skeletal Muscle

Muscle → Fascicles → Fibers → Myofibrils → Myofilaments (actin, myosin)

Skeletal muscle is composed of numerous muscle fascicles or bundles separated by connective tissue. Within each fascicle, there are numerous muscle fibers which are also separated by a thin layer of connective tissue. By electron microscopy, one can see the ultrastructural components of the muscle fiber: myofibrils with thick and thin filaments composed of myosin and actin respectively, the contractile proteins of muscle (Figures 20-1 and 20-2).

Connective Tissue
  • Epimysium: Connective tissue covering the outer surface of the muscle

  • Perimysium: Connective tissue between and surrounding muscle fascicles; contains small arteries, veins, and nerves

  • Endomysium: Connective tissue surrounding individual muscle fibers within the fascicles

Muscle Fiber
  • Elongated multinucleated cell

  • Sarcolemma: Plasma membrane surrounding each fiber

  • Sarcoplasm: Specialized cytoplasm of a muscle cell containing different organelles

  • Nuclei and mitochondria, located just beneath the sarcolemma

  • Myofibrils: Composed of thick (myosin) and thin filaments (actin) arranged in sarcomeres

  • Sarcoplasmic reticulum: Fenestrated membrane system extending between myofibrils responsible for the release and uptake of calcium ions during muscle contraction and relaxation

  • Transverse tubule system: Depolarization occurs through this branched tubular system running transversely along the fiber.

Muscle Fiber Types

Muscle fibers are divided into different types based on specific characteristics and can be found in different concentrations in different muscles throughout the body. By light microscopy, muscles form a mosaic or checkerboard pattern of different fiber types.

  • Type 1: Slow-twitch, oxidative

  • Type 2A: Fast-twitch, oxidative-glycolytic

  • Type 2B: Fast-twitch, glycolytic

  • Type 2C: Undifferentiated

Type 1 fibers have the following properties:

  • Loaded with mitochondria

  • Depend on cellular respiration for ATP

  • Fatty acids are the main energy source

  • Resistant to fatigue

  • Rich in myoglobin (red meat)

  • Activated by small diameter, slow conducting motor neurons

  • Slow twitch fibers

  • Muscles used in activities requiring endurance

Type 2 fibers have the following properties:

  • Few mitochondria

  • Rich in glycogen

  • Depend on creatine phosphate and glycolysis for ATP production

  • Low in myoglobin (white meat)

  • Activated by large diameter fast conducting motor neurons

  • Fast twitch fibers

  • Rapid and forceful movement


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 ...

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