Skeletal muscle system disease

1. Skeletal muscle system disease Prepared by: Siti Norhaiza Binti Hadzir

2. 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.

5. 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.

6. 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").

7. 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

8. 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.

9. Causes of myopathy

10. 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.

11. 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).

12. 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.

13. Investigation of Rhabdomyolisis • Total creatine kinase in serum • Urine myoglobin • Serum potassium • Serum calcium • Serum creatinine

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

15. 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 Dunchenne’s disease. • Dystropin is a membrane-associated structural protein that serves as a strut to maintain muscle fiber integrity during contraction

16. 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.

17. 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.

18. Inflammation of muscle (Myositis) • Infectious disease (bacteria, viral, parasitic, exotoxic • Immune disease (SLE) • Other causes (radiation, ischemia)

19. 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.

20. 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

21. 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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