Muscle

• Muscle tissue is responsible for body movements. Consists of elongated cells characterised by the presence of great numbers of contractile cytoplasmic filaments.

  Muscle cells are mesodermal in origin.

  3 types based on morphologic and functional characteristics:

  • Skeletal
  • Smooth
  • Cardiac

   
• Skeletal

  Consists of bundles of very long up to 4cm, cylindrical multinucleated cells with a diameter of 10-100um called muscle fibres

  Oval nuclei found at periphery of cell. Characteristic nuclear location is used to distinguish skeletal muscle
• Smooth

  Composed of long, 30-200um, spindle-like cells which in cross section appear narrow, 5-10um circular profiles.

  Each cell possesses a centrally located elongated nucleus.

  In bundles of smooth, the fusiform cells overlap along their length. Normally organised into layers, with cells in adjacent layers usually lying at right angles to each other.

  May group to form small muscle bundles, - arrector pili muscles in skin

  Contractions of smooth muscle are relatively slow and cell may remain contracted for long periods without fatigue. Cells may undergo partial or wavelike contractions.
• Cardiac

  Mature cells exhibit a cross striated banding pattern identical to skeletal. However, each cell possesses only one or two centrally located nuclei.

  Surrounding the columns of muscle cells is a delicate sheath of connective tissue which lies a rich capillary network.

  A unique and distinguishing characteristic is the presence of darkly staining transverse lines that cross the chains of cardiac cells at irregular intervals. These intercalated discs represent junctional complexes found at the interface between adjacent cardiac myocytes
• Ion channel myopathies

  • Group of familial diseases characterised clinically by myotonia, relapsing episodes of hypotonic paralysis (induced by vigorous exercise, cold or high carb meal or both).
  • Hypotonia variants associated with elevated, depressed or normal serum potassium levels at time of attack are called hyperkalaemic, hypokalaemic and normokalaemic periodic paralysis
• Congenital myopathies

  • Group of disorders defined largely on the basis of the pathologic findings within muscle
  • Most conditions share common clinical features, incl. onset early in life, non-progressive or slowly progressive course, proximal or generalised muscle weakness and hypotonia.
• Myopathies associated with inborn errors of metabolism

  • Many associated with metabolic disease are found in the setting of disorders of glycogen synthesis and degradation
  • Combinations of clinical, pathologic and molecular information are used to arrive at a specific diagnosis
  • Myopathies can also result from disorders of mitochondrial function
• Lipid Myopathies

  • Abnormalities of the carnitine transport system or deficiencies of the mitochondrial dehydrogenase enzyme systems can lead to accumulation of lipid droplets within muscle
  • The principle morphologic characteristic is accumulation of lipid within myocytes
  • The myofibrils are separated by vacuoles that stain with oil red O or Sudan Black and have the typical appearance of lipid by electron microscopy
  • The vacuoles occur predominantly in type I fibres and are dispersed diffusely throughout the fibre
• Mitochondrial Myopathies

  • Mutations in both nuclear and mitochondrial genes
  • Diseases that involve the MTDNA show material inheritance
  • Present in young adulthood and manifest with proximal muscle weakness, sometimes with severe involvement of the muscles that move the eyes.
  • Most consistent pathogenic finding in skeletal muscle is aggregates of abnormal mitochondria that are demonstrable only by special techniques
  • Abnormal mitochondria impart a blotchy red appearance to the muscle fibre on the modified gomori trichrome stain
  • Also have a distinctive appearance electron microscopically
• Inflammatory Myopathies

  • 3 subgroups:
  • Infectious
  • Non-infectious
  • Systemic inflammatory disease
  • Comprise an uncommon, heterogenous group of disorders characterised by injury and inflammation of mainly skeletal muscles
  • 3 distinct disorders
  • Dermatomyositis
  • Polymyositis
  • Inclusion-body myositis
  • May occur alone or with other immune-mediated diseases, particularly systemic sclerosis
• Denervation Atrophy

  Neurogenic atrophy of muscle is caused by any process that affects the anterior horn cell or its axon in the peripheral nervous system

  Denervation of muscle leads to breakdown of myosin and actin, with a decrease in cell size and resorption of myofibrils but cells remain viable

  Type specific atrophy is characteristic of some disease states

  Type II fibre atrophy is a relatively common finding and is associated with inactivity or disuse
• Skeletal Muscle Pathologies

  Almost all malignant

  Rhabdomyosarcoma

  Most common soft tissue sarcoma of childhood and adolescence, usually appears before age 20. may arise in any anatomic location, but most occur in the head and neck or the genitourinary tract, where there is little, if any, skeletal muscle as a normal constituent. Only in extremities do they appear in relation to skeletal muscle.

  Histologically sub-classified into the embryonal, alveolar and pleomorphic variants.

  Immunohistochemically they stain with antibodies to the myogenic markers such as desmin, MYO-D1 and myogenin
• Cardiac Muscle Pathologies

  Cardiomyopathy - heart disease resulting from a primary abnormality in myocardium.

  Most cases they are idiopathic, major advance in understanding of myocardial diseases show specific genetic abnormalities in cardiac energy metabolism or structural and contractile proteins underline myocardial dysfunction in many patients.
• Cardiac myxoma

  Myxoma: most common primary tumour of the heart.

  • Benign tumours
  • Surgical removal is usually curative
  • ~10% of patients with myxoma have a familial cardiac myxoma syndrome

   
• Other common primary tumours of the heart are:

  • Lipoma
  • Papillary fibroelastoma
  • Rhabdomyoma
  • Sarcoma
• Muscle Enzyme Histochemistry


  Done on fresh tissue samples, with sections cut by frozen section
• Specimen collection


  • Usually obtained by open surgical biopsy, with a laboratory scientist in attendance to correctly handle the specimen
• Skeletal muscle fibre types

  • Type I (light)
  • Type II (dark): IIA, IIB, IIC
• Type I fibres (slow-twitch)

  Use predominantly an aerobic metabolism, contain abundant mitochondria, lipid and myoglobin, and have a good blood supply
• Type II fibres (fast-twitch)

  Have an anaerobic metabolism, contain only a few mitochondria and have less blood supply, are rich in glycogen and glycolytic enzymes, and have a high resistance to fatigue
• Adenosine triphosphatase (ATPase) method


  Used to divide type II fibres into their 3 sub-types