‫بسم هللا الرحمن الرحيم‬

Muscle disorders
2024

Dr Bashar Hassawi
 Learning Objectives (LO)
1. Describe the process of skeletal muscle remodelling and its relevance
to atrophy and hypertrophy.
2. Outline the physiology of the neuromuscular junction and describe
the pathogenesis and clinical features of myasthenia gravis.
3. State how neuromuscular transmission is disrupted in botulism and
organophosphate poisoning.
4. Describe the pathophysiology of Duchenne muscular dystrophy.
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Muscle disorders:
1. Injury (Trauma) or overuse, such as sprains or strains, cramps or
tendinitis.
2. Diseases of nerves that affect muscles (Muscle lesion secondary to
nerve injury).
3. Genetic disorder, such as muuscular dystrophies.
4. Inflammation, such as myositis and other autoimmune diseases.
5. Alteration in neuromuscular transmission.
6. Infections.
7. Tumors.
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Remodeling of Muscles
Skeletal muscle is a dynamic tissue that responds adaptively to the nature
and intensity of muscle use.
Although skeletal muscle has a remarkable capacity to repair and adapt to
exercise and injuries induced muscle damage, the remodeling capacity of
skeletal muscle is not well known. However, there is evidence to suggest
that athletes who expose their muscles to vigorous training and racing
regimes may exceed the muscles capacity for adaptation.

Adaptation:
1- Muscle atrophy: Refers to the decrease in muscle mass (Size) leading to
muscle weakness or a decrease in the ability to generate force.

2- Muscle hypertrophy: Refrers to an increase in size of skeletal muscle

through a growth in size of its component cells. Two factors contribute to
hypertrophy:
a. Sarcoplasmic hypertrophy, which focuses more on increased muscle
glycogen storage.
b. Myofibrillar hypertrophy, which focuses more on increased myofibril size.
 LO 1 Disuse atrophy: Often occurs from not using a muscle, The condition
often occurs after a period of bed rest after a major surgical procedure
(immobilization), people with limbs in casts. The older population is particularly at
risk for developing disuse atrophy from becoming bedridden due to chronic illness or
aging, as well as those who suffer from a joint disease that causes them to become
immobile. Other cause is a disconnection of the nerve signals to the muscle
(Denervation atrophy).
Muscle atrophy occurs by a change in the normal balance between protein synthesis
and protein degradation. During atrophy, a down-regulation of protein synthesis
pathways occurs, and an activation of protein degradation leads to fiber atrophy and
loss of power.

Poliomyelitis
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• Most common causes of lower motor neuron injuries are trauma to peripheral
nerves that cut the axons and virus that selectively attacks ventral horn cells like
poliomyelitis. Other causes include Guillain–Barré syndrome, (Bacterial infection)
= C. botulism,, and cauda equina syndrome.
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Sarcopenia: Age-related loss of skeletal

muscle. Often found together with
osteoporosis.
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Disorders of the Neuromuscular Junction
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Disorders of the Neuromuscular Junction

Myasthenia gravis
Definition
An autoimmune disease due to an antibody mediated attack directed
against nicotinic AchR at neuromuscular junction

Causes:
• 70% have thymic hyperplasia
• 10% have thymoma
• Unknown
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Myasthenia gravis
Clinical features: The hallmark of myasthenia gravis is fatigability.
Muscles become progressively weakness during periods of activity and
improve after periods of rest.

First noticeable symptom is weakness of the eye muscles that control

eye and eyelid movement (drooping of eyelids with double vision).

In others, difficulty in swallowing, chewing and talking (slurred

speech) may be the first signs, facial expressions.

The muscles that control breathing and neck

and limb movements can also be affected.
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Synaptic antigens: The antibodies in MG attack the nicotinic

acetylcholine receptor, or a related protein called MuSK a muscle-
specific kinase.

nerve

VGCC: voltage gate calcium cha

muscle
MuSK AChR 14
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Women at higher
incidence 3 : 2

Majority of the MG
are young women in
the third decade and
middle aged men in
5th and 6th decade

Children account for

11% of all patients
with MG
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Diagnostic tests

• Electromyography

• Anti AChR antibodies

• MRI of mediastinum – thymomas, hyperplasia

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Botulism is a rare and potentially fatal paralytic illness caused by a toxin

produced by the bacteria Clostridium botulinum (block Ach release).
The disease begins with weakness, trouble seeing, feeling tired, and
trouble speaking. This may then be followed by weakness of the arms,
chest muscles and legs. The disease does not usually affect
consciousness.

Organophosphate poisoning:
Organophosphates inhibit acetylcholinesterase, so the inhibition of
this enzyme, which causes acetylcholine accumulation, results in
Overstimulation of nicotinic acetylcholine receptors and muscle
overstimulation; in the central nervous system.
Results in anxiety, headache, convulsions, ataxia, depression of
respiration and circulation, tremor, followed by general weakness, and
potentially coma.
 Muscular dystrophy
Is a collection of inherited diseases (Genetic) characterized by skeletal
muscle weakness and degeneration. defects in muscle proteins called
dystrophin.

Muscular dystrophies are progressive disorders because over time

healthy muscle fibers are lost (death of muscle cells ) and replaced by
fibrosis and fat, patients experience weakness, although muscle
groups may be targeted differently in specific forms of muscular
dystrophy.

Respiratory failure, resulting from the weakening of breathing

muscles, may limit lifespan in muscular dystrophy unless mechanical
support is instituted.
In some forms of muscular dystrophy, the heart is also affected resulting
in cardiac complications including heart failure and irregular heart
rhythms.
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Types of Muscular Dystrophy:

▪ Duchenne/Becker (DMD/BMD)
▪ Myotonic (MMD)
▪ Limb-Girdle (LGMD)
▪ Facioscapulohumeral (FSH)
▪ Congenital (CMD) myopathies
▪ Distal (DD)
▪ Oculopharyngeal (OPMD)
▪ Emery-Dreifuss (EDMD)
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Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is one of the most common
forms of muscular dystrophy. DMD is caused by recessive
mutations in the dystrophin gene on X chromosome (X-
chromosome linked recessive)
leads to deficiency of dystrophin, resulting in progressive loss of
muscle fibers.
• First described in 1861.
• Dystrophin gene discovered in the early 1980's.
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Duchenne muscular dystrophy

• Affecting 1 in 3,500 to 5,000 newborn males worldwide. Boys with
DMD show signs of muscle weakness early in childhood, typically
between 2 and 7 years of age, but the girls are carriers
• Initial symptoms: difficulty getting up from deep position and
climbing steps, waddling gait.
• Weakness most pronounced in limb-girdle muscles, trunk
erectors; craniobulbar muscles are spared
• Skeletal deformities
• Cardiomyopathy
• Inability to walk by 9-11 years
• Death occurs usually in the 3rd decade, from respiratory
insufficiency
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Duchenne muscular dystrophy

Gower’s sign: The sign describes a patient that has to use their hands
and arms to "walk" up their own body from a squatting position due to
lack of hip and thigh muscle strength.
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Duchenne muscular dystrophy

Normal Duchenne dystrophy

Diagnosis:
•Lack of immunostaining of dystrophin in muscle biopsy specimen
•Demonstration of deletion in the dystrophin gene
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Becker muscular dystrophy (BMD) is also caused by mutations in the

DMD gene that encodes dystrophin, reduced amount of dystrophin.
Individuals with BMD share similar signs and symptoms with DMD
boys but with more benign course.
Like DMD, the heart can be affected in BMD.
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