Comprehensive Notes on Myopathies and Muscle Disorders

Myopathies

• Myopathies refer to diseases of the muscle, ranging from mild to life-threatening.

Types of Muscle Injuries

• Strain
  • Injury from overexertion or trauma.
  • Involves the musculotendinous unit (muscle and tendon).
  • Often accompanied by myalgia (muscle pain).
  • May result in inflammation of the muscle or tendon.
• Sprain
  • Injury near a joint involving ligament damage.
  • Does not involve the muscle and tendon.
• Cramps
  • Painful muscle spasms or involuntary twitches.
  • Example: Charlie horse in the calf muscle (gastrocnemius).
• Crush Injuries
  • Result from severe trauma.
  • May release cell contents of the muscle, potentially causing kidney failure if untreated. This is because the body reabsorbs these cellular contents.
• Stress-Induced Muscle Tension
  • Can cause headaches and back pain, often leading to migraines.
  • Combating tension:
    • Simple movement, especially during prolonged periods of studying or memorizing.
    • Common areas: between shoulder blades, base of the neck.

Muscle Infections

• Bacterial and viral infections can affect the muscle.
• Parasites can also affect the muscle.
• Polio (Poliomyelitis)
  • Viral infection of the motor nerves, ranging from mild to life-threatening.
  • Could cause death or irreversible paralysis.
  • Patients who survived needed the assistance of an iron lung to breathe.
  • Eradicated in the United States due to vaccination programs.

Muscular Dystrophy

• Group of genetic disorders characterized by muscle atrophy (shrinkage of the muscle).
• Duchenne Muscular Dystrophy (DMD) or Pseudohypertrophic Muscular Dystrophy
  • Most common type.
  • Characterized by rapid progression of weakness and atrophy.
  • Muscle is replaced by fatty connective tissue.
  • X-linked inherited disease primarily affecting genetic males due to having only one X chromosome.
  • Females with two affected X chromosomes can develop the disease, but it's less common.
• DMD Genetic Information
  • Affects approximately 1 in every $3,500$ to $5,000$ newborn boys.
  • Universally fatal disease.
  • Characterized by muscle weakness, leading to delayed walking, abnormal gait, and frequent falls.
  • Over time, children lose the ability to walk and typically succumb to respiratory or cardiac failure during their mid-twenties.
  • Within muscle, the protein dystrophin performs a critical structural role, anchoring the actin skeleton to the sarcolemma membrane in conjunction with other proteins of the dystroglycan complex.
  • Dystrophin is thought to help protect the muscle from strain related damage during muscle contraction.
  • DMD can be caused by a variety of mutations to the dystrophin gene, which is found on the X chromosome. Mutations can lead to a lack of dystrophin, which results in muscle damage, degeneration and loss.
  • The dystrophin gene is one of the longest human genes, spanning approximately $2,500,000$ bases and comprised of $79$ different protein coding segments, termed exons, which are interspersed amongst introns.
  • To generate the dystrophin protein, the cell must first transcribe the entire length of the dystrophin gene into pre mRNA.
  • Within the cell, specialized cellular machinery known as the spliceosome binds specific sequences on the pre mRNA and removes the introns to produce the mature mRNA.
  • The dystrophin mRNA is translated by the ribosome using a reading frame that reads the mRNA three nucleotides at a time.
  • Each three nucleotide sequence is called a codon, and each codon is translated into one amino acid.
  • Most commonly, DMD is caused by frameshift mutations due to deletions of one or more exons from the dystrophin gene.
  • In these cases, the exons following the deletion are misaligned or out of frame, preventing translation of a functional dystrophin protein.
  • Such frameshift mutations result in production of little or no functional dystrophin protein.
  • Lack of dystrophin leads to a cycle of muscle cell degeneration, inflammation, and fibrosis that is characterized by loss of muscle mass and muscle wasting.

Myasthenia Gravis

• Autoimmune muscle disease characterized by weakness and chronic fatigue.
• Commonly affects the face (smoothing of the forehead, eyebrow droop, drooping of the corner of the mouth).
• Caused by a lack of communication between nerves and muscles.
• Error in the transmission of nerve impulses to the muscles at the neuromuscular junction.
• Neuromuscular Junction
  • The space between nerves and muscles.
  • Neurotransmitters (chemicals) communicate from nerves to muscles to signal them what to do.
  • Acetylcholine is the neurotransmitter released by motor nerves.
  • Acetylcholine travels to receptors on the muscle, triggering muscle contraction.
• Myasthenia Gravis Mechanism
  • Antibodies (immune proteins) alter or destroy the receptors for acetylcholine at the neuromuscular junction.
  • Without working receptors, acetylcholine can't function, leading to paralysis.
  • Most cases are caused by antibodies blocking acetylcholine receptors.
  • Antibodies to other proteins like muscle-specific kinase (MuSK) can also impair transmission at the neuromuscular junction.
• Autoimmune Nature
  • In autoimmune diseases, the body's immune system attacks its own tissues.
  • Thymus Gland: The thymus gland, which controls immune function, may be associated with myasthenia gravis.
  • The thymus gland typically atrophies in adulthood but may be involved in producing the antibodies that attack acetylcholine receptors.

Muscular Degenerative Disease

• In muscular degenerative disease the muscle is degenerating.