Review of Muscular System
1
Muscle
• Skeletal muscle
– > 600 muscles in body
• Cardiac muscle
• Smooth muscle
2
Muscle cell structure
• Sarcolemma
motor end plate
transverse ( T- ) tubules
• Sarcoplasm
• Sarcoplasmic Reticulum – Stores Ca++
3
Global view of a neuromuscular junction:
1. Axon
2. Motor end-plate
3. Muscle fiber
4. Myofibril
5
6
• Proteins:
– Thick filaments – myosin
– Thin filaments – actin
• Troponin
• Tropomyosin
– Sliding Filament Model
7
9
10
12
13
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 3,500 live male births
• Affects males
• Gene located on the short arm of the X
chromosome.
14
Muscular Dystrophy
Muscular Dystrophy
X-linked recessive defect
• 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.
19
Clinical Manifestations
• Fibrosis → contracture distorts skeletal
development
– Lordosis
– Scoliosis
– Compromised respiration
• Respiratory insufficiency
– Respiratory infection
• Cardiac muscle
– Dysrythmias
– Congestive heart failure
• Mental sluggishness
20
• Dystrophin is
lacking
– Membrane
damage
– Replaced by
fibrous
connective
tissue and
fatty deposits
22
• Therapy
– Passive stretching, splints to prevent
deformities
– Sustain mobility
– Sustain respiratory function
– Possibly gene therapy
24
Myasthenia gravis
• Autoimmune disease in which antibodies
(IgG) bind with acetylcholine receptors on
muscle cells. (T-lyphmocyte abnormalities)
• 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
25
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
26
• Cause is unknown.
• 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
30
Classification of myasthenia
‫الوهن العضلي‬
Congenital Myasthenia Gravis
This non-immune form of myasthenia gravis is a very rare
form of myasthenia gravis. This is caused by an autosomal
recessive disease that means, both parents need to have
copies of this gene. When both these copies are inherited by
the infant it will lead to congenital myasthenia gravis. The
congenital myasthenia gravis symptoms in children are
usually seen after about a year of the baby's birth and remain
for life.
Classification of myasthenia
Transient Neonatal Myasthenia Gravis
This is a temporary form of myasthenia gravis. It is seen that
10 to 15% of babies that are born to mothers with
myasthenia gravis are affected with this condition. The
transient neonatal myasthenia gravis symptoms in children
last only for a few weeks and clear away as soon as the
antibodies clear away. There is a very minimum risk of the
child developing myasthenia gravis later on in childhood or
adulthood.
Juvenile Myasthenia Gravis
This form of myasthenia gravis is an autoimmune disorder
that is commonly seen in female adolescents. This is a life
long disorder and the patient may keep going in and out of
remission
Classification of myasthenia
• Ocular myasthenia
– More common in males
– Weakness of eye muscles and eyelids, may
also include swallowing difficulties and slurred
speech
33
• Generalized autoimmune myasthenia
– Involves proximal (‫ )الدانية‬musculature
throughout the body, and has several courses
(‫)بالطبع‬:
• A course with periodic remissions (‫)غفران‬
• Slowly progressive (‫ )تقدمية‬course
• Rapidly progressive course
• Fulminating course (Develop suddenly and
severely)
34
Clinical manifestations
• Onset typically insidious (working or spreading in a
hidden and usually injurious way)
• 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
36
Clinical manifestations
• Muscles of the eyes, face, mouth, throat and
neck are usually affected first
– Levator and extraocular muscles affected most –
Diplopia (double vision), ptosis (dropping
eyelids), and ocular palsies (Paralysis)
– Muscles of facial expression, mastication,
swallowing and speech are the next most
involved
• Facial droop, expressionless face; difficulties in
chewing and swallowing,episodes of choking and
aspiration (Expulsion of breath in speech)
• Nasal, low volume, high-pitched monotonous speech
pattern
37
levator palpebrae superioris muscle
Facial droop
• 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
39
Myasthenic crisis
• Severe weakness causes quadriparesis or
quadriplegia, respiratory insufficiency and
extreme difficulty in swallowing
40
Cholinergic crisis
A cholinergic crisis is an over-stimulation at a neuromuscular junction
due to an excess of acetylcholine (ACh), as of a result of the inactivity
(perhaps even inhibition) of the acetylcholine esterase (AChE) enzyme,
which normally breaks down acetylcholine.
• Anticholinesterase drug toxicity
• Intestinal motility increases
• Fasciculation ("muscle twitch", is a small, local, involuntary muscle
contraction and relaxation visible under the skin arising from the spontaneous
discharge of a bundle of skeletal muscle fibers (muscle fascicle).
•
•
•
•
Bradycardia
Pupillary constriction
Increased salivation
Increased sweating
41
Evaluation
• Improvement with edrophonium chloride
(Telison) for several minutes
• EMG – can be used to detect abnormal electrical activity of
muscle that can occur in many diseases and conditions
Antiacetylcholine receptor antibody titers
• Antistriated muscle antibody titers
• MRI to rule out thymoma
42
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
43
Treatment
•
•
•
•
•
•
Anticholinesterase drugs
Steroids
Immunosuppressant drugs
Cyclophosphamide
Plasmapheresis during myasthenic crisis
Thymectomy is treatment of choice for
individuals with thymoma
44