1 Review of Musculoskeletal System Chapter 18

2 Muscle Skeletal muscle > 600 muscles in body Fascia –Epimysium – forms tendons at ends –Perimysium – divides into fascicles –Endomysium – surrounds individual fibers

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4 Motor Unit One motor neuron and all the muscle fibers it innervates recruitment

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6 Muscle cell structure Sarcolemma motor end plate transverse ( t- ) tubules Sarcoplasm Sarcoplasmic Reticulum – Stores Ca ++

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9 Proteins: –Thick filaments – myosin –Thin filaments – actin Troponin Tropomyosin –Sliding Filament Model

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14 Muscular Dystrophy Group of rare diseases characterized by a genetic etiology and progressive degeneration of skeletal muscle. X-linked recessive defect Most common of the muscular dystrophies 1 in 3,000 live births Affects males Gene located on the short arm of the X chromosome.

15 30% of cases arise as a new mutation Can be diagnosed immediately after birth by high serum creatine kinase Muscle weakness and delayed motor skills can be detected early – obvious by age 5 Age 10 – require leg bracing Age 12 – wheelchair Age 15 completely bedridden Death by 20 – 30 of cardiac arrest or respiratory failure.

16 Fibrosis → contracture distorts skeletal development –Lordosis –Scoliosis –Compromised respiration Respiratory insufficiency –Respiratory infection Cardiac muscle –Dysrythmias –Congestive heart failure Mental sluggishness

17 Dystrophin is lacking –Membrane damage –Replaced by fibrous connective tissue and fatty deposits Therapy –Sustain mobility –Sustain respiratory function

18 Myesthenia gravis Autoimmune disease in which antibodies (IgG) bind with acetylcholine receptors on muscle cells. Reduces the number of acetylcholine receptors at the neuromuscular junction Characterized by muscle weakness and fatigability Also associated with other autoimmune disorders, such as SLE, rheumatoid arthritis, and thyrotoxicosis

19 In 10-25% of people with MG thymic tumors are found –More common in males than females 70 – 80 % have pathologic changes in the thymus

20 Classification of myasthenia Neonatal myasthenia –Transitory condition in which % of infants born to mothers with MG show symptoms of the disease Congenital myasthenia Juvenile myasthenia – onset us.about 10 years Ocular myasthenia –More common in males –Weakness of eye muscles and eyelids, may also include swallowing difficulties and slurred speech

21 Generalized autoimmune myasthenia –Involves proximal musculature throughout the body, and has several courses: A course with periodic remissions Slowly progressive course Rapidly progressive course Fulminating course

22 Pathophysiology Defect in the nerve impulse transmission at the NMJ Postsynaptic acetylcholine receptors are no longer recognized as “self” and antibodies are produced against them. IgG blocks the binding of ACh Eventually destroys the receptor Causes diminished transmission of nerve impulse across the NMJ and lack of muscle depolarization Cause is unknown.

23 Clinical manifestations Onset typically insidious May first appear during pregnancy, postpartum or with the administration of certain anesthetic agents Complaints are fatigue and progressive muscle weakness –Fatigue after exercise –Recent history of recurrent upper respiratory infections

24 Clinical manifestations Muscles of the eyes, face, mouth, throat and neck are usually affected first –Levator and extraocular muscles affected most - Diplopia, ptosis, and ocular palsies –Muscles of facial expression, mastication, swallowing and speech are the next most involved Facial droop, expressionless face; difficulties in chewing and swallowing, drooling, episodes of choking and aspiration Nasal, low volume, high-pitched monotonous speech pattern

25 Less frequently involved are the muscles of the neck, shoulder girdle and hip flexors –Fatigue requires periods of rest –Weakness of arms and legs –Difficulty maintaining head position –Respiratory muscles of chest wall and diaphragm become weak In advanced stage all muscles are weak

26 Myasthenic crisis Severe weakness causes quadriparesis or quadriplegia, respiratory insufficiency and extreme difficulty in swallowing

27 Cholinergic crisis Anticholinesterase drug toxicity Intestinal motility increases Fasciculation Bradycardia Pupillary constriction Increased salivation Increased sweating

28 Evaluation Improvement with edrophonium chloride (Telison) for several minutes EMG – amplitude of action potentials declines Antiacetylcholine receptor antibody titers Antistriated muscle antibody titers MRI to rule out thymoma

29 Progression Varies Appears first as a mild case that spontaneously remits with a series of relapses and symptom free intervals Over time can progress leading to death Ocular myasthenia has a good prognosis

30 Treatment Anticholinesterase drugs Steroids Immunosuppressant drugs Cyclophosphamide Plasmapheresis during myasthenic crisis Thymectomy is treatment of choice for individuals with thymoma