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PH-MS13

Primary muscle diseases

How faults in the muscle fibre itself cause weakness: a missing dystrophin anchor in Duchenne dystrophy, a toxic RNA repeat in myotonic dystrophy, failing fuel in metabolic myopathies, and drugs or injury that break fibres down.

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  • 6 steps · 10 questions
  • 3D anatomy, affected parts marked

By the end, you can

  • Describe the normal muscle fibre: its dystrophin anchor, its fuels and how its motor units are arranged.
  • Explain how loss of dystrophin causes cycles of necrosis and regeneration, and why Duchenne and Becker dystrophy differ in severity.
  • Explain how an expanded CTG repeat causes myotonia and the many organ features of myotonic dystrophy, and why it can worsen across generations.
  • Relate failures of glycogen, fat and mitochondrial metabolism, and injury by statins and glucocorticoids, to their patterns of weakness and exercise intolerance.
  • Explain how rhabdomyolysis leads to hyperkalaemia and acute kidney injury.
  • Tell myopathic from neurogenic weakness on examination, EMG and biopsy, recognise the key tests and numbers, and explain how the main treatments act on each mechanism.

What it is

Primary muscle diseases (myopathies) are disorders in which the fault lies in the skeletal muscle fibre itself, not in its nerve or the neuromuscular junction. They include inherited muscular dystrophies (progressive degeneration of fibres, such as Duchenne and myotonic dystrophy), metabolic and mitochondrial myopathies (failing energy supply) and acquired myopathies caused by drugs, toxins and hormones. Rhabdomyolysis is the acute breakdown of muscle from any cause. The inflammatory myopathies have their own lesson.

5 types to tell apart
Dystrophinopathies (Duchenne and Becker)
X-linked loss (Duchenne) or reduction (Becker) of dystrophin, so the fibre membrane tears with use.
Other muscular dystrophies
Limb-girdle dystrophies (many genes, mostly for proteins of the membrane complex or its repair) and facioscapulohumeral dystrophy; myotonic dystrophy, in which a repeat expansion makes a toxic RNA.
Metabolic and mitochondrial myopathies
Fibres are built normally but cannot use glycogen (McArdle, Pompe), fat (carnitine palmitoyltransferase II deficiency) or oxidative phosphorylation (mitochondrial disease).
Toxic and endocrine myopathies
Statins, glucocorticoids and alcohol each injure muscle in a different way; an underactive thyroid also weakens muscle and raises creatine kinase.
Rhabdomyolysis
Acute breakdown of many fibres at once, from crush, exertion, heat, drugs, toxins or an underlying myopathy.

US spelling: fibre → fiber, fibres → fibers.

Normal function

The muscle fibre, its anchor and its fuel

Each skeletal muscle fibre is a single long cell with many pressed to its edge, wrapped in a thin sheath of beside its . Its contractile proteins are stacked in sarcomeres that give the alternating and bands. Just inside the fibre membrane (the sarcolemma), the large protein dystrophin ties the actin of the cytoskeleton to a complex of glycoproteins (dystroglycan and the sarcoglycans) that crosses the membrane and binds laminin in the basal lamina outside. This link spreads the force of each contraction and protects the membrane from tearing.

Fibres burn several fuels. A brief burst runs on ATP and phosphocreatine, whose phosphate creatine kinase (CK) transfers to ADP. Within seconds, myophosphorylase releases glucose units from stored glycogen for glycolysis. Long, steady work is fuelled by fatty acids, carried into the mitochondria by carnitine palmitoyltransferase and oxidised there. CK, myoglobin and potassium stay inside an intact fibre.

One motor neurone supplies a motor unit of fibres scattered among those of other units, all of one type: type 1 (slow, oxidative, resistant to fatigue) or type 2 (fast, glycolytic). Stained for fibre type, normal muscle is a checkerboard. Damaged fibres are replaced from satellite cells, stem cells that lie under the basal lamina.

Point to it on the model