Skeletal muscle system disease

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Skeletal muscle system disease

• Prepared by Siti Norhaiza Binti Hadzir

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Normal skeletal muscle

• It is composed of fascicles of muscle fibers
  (myofibrils) that represent the cellular unit.
• A myofibril is a long, cylindric, multinucleate
  cell that is the contractile unit of the muscle.

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Line A show the width of one cell (fiber). Note
the striations characteristics of this muscle
type. These cells are multicellular, B marks one
nucleus.
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Muscle Disease-Introduction

• Myopathy- neuromuscular disease in which the
  muscle fibers do not function for any one of many
  reasons, resulting in muscular weakness.
• "Myopathy" simply means muscle disease (myo-
  Greek "muscle" patho-Greek "suffering").

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Muscle disease- Diagnosis

• General clinical considerations- family history,
  age of onsets, history of drugs, distribution of
  muscle weakness and rate of progression.
• Special investigation of neuromuscular electrical
  activity (electromyograph)
• Laboratory test- muscle biopsy
• - serum enzymes (CK)
• - chromosomal analysis

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Muscle weakness

• Inability to exert force to the degree that would
  be expected given the individual's general
  physical fitness.
• Occur due to lack of energy producing molecules
  or a failure in the balance of electrolytes
  within and surrounding the muscle cell necessary
  for neuromuscular function.

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Causes of myopathy
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Rhabdomyolysis

• Normal muscle which is overused will end up weak
  or spasm until rested.
• In severe cases of overuse, especially where
  movements are strong and erratic as might occur
  during convulsions, damage to muscle cells may
  result.
• Severe damages muscle cells release myoglobin, a
  condition known as rhabdomyolisis.

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Biochemical Changes in Rhabdomyolysis

• Damage muscle cells will leak myoglobin into the
  plasma.
• Release myoglobin in plasma will be filtered at
  the glomerulus and cause an orange and brown
  color.
• Myoglobinuria must be distinguished from
  hematuria (the urine contains no RBC in
  myoglobinuria) and hemoglobinuria (by immunoassay
  or spectroscopy).

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• The damage muscle cells release large amounts of
  K into the extracellular fluid causing
  hyperkalemia.
• Damage cell tend to take up calcium ions,
  reducing serum calcium concentration
  (hypocalcemia).
• Severe muscle damage is frequently accompanied by
  a reduction in blood volume.
• This is due to hemorrhage in severe trauma, or
  indirectly because of fluid sequestration in the
  damaged tissue.

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Investigation of Rhabdomyolisis

• Total creatine kinase in serum
• Urine myoglobin
• Serum potassium
• Serum calcium
• Serum creatinine

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Skeletal muscle disorders

• Primary muscle disease e.g muscular dystrophies
• Inflammation of muscle (myositis)
• Disorders of neuromuscular Transmission
  (Myasthenia Gravis)

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Duchenne Muscular Dystrophy (DMD)

• The disease is due to the absence of a gene
  located on the short arm of the X chromosome at
  the Xp21 site.
• This results in the absence of the gene product
  dystropin in skeletal muscle, a consistent
  finding in Dunchennes disease.
• Dystropin is a membrane-associated structural
  protein that serves as a strut to maintain muscle
  fiber integrity during contraction

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The progression of the disease

• Affected person (male) are normal at birth and
  manifest the disease in early childhood.
• 1st affects the muscle of the pelvic girdle
  (difficult getting up from seated position)
• Walking is difficult (have to use wheelchair)
• Death commonly results from involvement of
  respiratory muscles.

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Investigation of DMD

• A positive Gower's sign reflects the more severe
  impairment of the lower extremities muscles. The
  child helps himself to get up with upper
  extremities first by rising to stand on his arms
  and knees, and then "walking" his hands up his
  legs to stand upright.
• Creatine kinase (CK-MM) levels in the bloodstream
  are extremely high.
• An electromyography (EMG) shows that weakness is
  caused by destruction of muscle tissue rather
  than by damage to nerves.
• Genetic testing can reveal genetic errors in the
  Xp21 gene.
• A muscle biopsy (immunohistochemistry or
  immunoblotting) or genetic test (blood test)
  confirms the absence of dystrophin.

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Inflammation of muscle (Myositis)

• Infectious disease (bacteria, viral, parasitic,
  exotoxic
• Immune disease (SLE)
• Other causes (radiation, ischemia)

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Disorders of Neuromuscular Transmission

• Myasthenia Gravis is a clinical syndrome
  resulting from failure of neuromuscular
  transmission due to blockage and destruction of
  acetylcholine receptors by autoantibody.
• Myasthenia gravis is therefore an organ-specific
  autoimmune disease.
• MG is characterized by muscle weakness that is
  typically aggravated by repeated contraction.

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Myasthenia Gravis

• Muscle with the smallest motor units are affected
  first, the most typical clinical presentation
  being weakness of ocular muscles causing drooping
  of the eyelid
• The disease sometimes progress to include facial
  muscles, limb girdle muscles, and respiratory
  muscles

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Diagnosis of MG

• Edrophonium (Tensilon)-short acting drug produce
  immediate improvement in muscle weakness when
  administered IV
• EMG-? in amplitude of muscle action potentials
  when muscle is subjected to repeated voluntary
  contraction
• Serum assay for anti-Ach receptor antibody

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Myositis Dystrophies MG Myopathies
CK -
Aldolase -
Amino-transferase -
LDH -
Other useful test Biopsy EMG, biopsy EMG, Ach-receptor Ab EMG, biopsy
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