Pneumonia
Skeletal muscle diseases
1
Pneumonia
Skeletal muscle diseases
a. Discuss the muscular dystrophies.
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- Describe their pathogenesis.
- Describe their morphology.
- Discuss their clinical picture and
management.
b. Discuss the disease of neuromuscular
junctions.
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- Describe their pathogenesis.
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- Discuss their morphology.
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- Discuss the clinical picture and
management.
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Reference: Robbins Basic Pathology, 8th edition (pages 827 – 830).
2
Pneumonia
Diseases of Muscles
Myopathies: disorders of muscle fibres
 Dystrophy: a genetic myopathy.
 Neurogenic: interference with nerve supply.
 Bilateral & symmetrical: myopathy
 Asymmetric: neurogenic.
 Diagnosis:
- Clinical. – Muscle biopsy. - Nerve conduction.
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3
a. Discuss the muscular dystrophies.
Definition
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Muscular dystrophy is a heterogeneous group of
inherited disorders recognized by progressive
degenerative muscle weakness and loss of
muscle tissue (started in childhood).
Affect muscles strength and action.
Generalized or localized.
Skeletal muscle and other organs may involve
Limitation: Difficulties with walking or Maintaining posture,
Muscle spasms. Neurological, Behavioral, Cardiac, or other
Functional limitations.
a. Discuss the muscular dystrophies.
Definition
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Muscular dystrophy
Causes
Inheritance
 Dominant genes
 Recessive gene
Depends on the age when symptoms appear, and the
types of symptoms that develop.
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Risk
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Because these are inherited disorders, risk include a
family history of muscular dystrophy
How Many People Are Affected
It is estimated that between 50,000 -250,000 are
affected annually. 1 per 3500 live male births
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Who Discovered Muscular Dystrophy
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Each neuromuscular disease (muscular dystrophy)
was discovered by different person.
43 Types of Neuromuscular Diseases e.g:
1- X-Linked Muscular Dystrophy (Duchenne Muscular Dystrophy- DMS)
2- Becker Muscular Dystrophy- BMS
3- Myotonic Dystrophy.
2- Other Muscular Dystrophies:
Less common, share many features with DMS, BMS, affect certain
muscle groups (Fascioscapulohumeral muscular dystrophy;
autosomal dominant\Oculopharyngeal muscular dystrophy;
autosomal dominant, Congenital muscular dystrophies; autosomal
recessive etc..).
Muscular dystrophies- Pathogenesis
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DMS& BMS:
1- Caused by abnormalities in DMD, a gene that is located in the Xp21
region It encodes a 427-kD protein named dystrophin.
2- The genetic abnormalities are deletions with point mutations accounting
for the rest.
Approximately two thirds of the cases are familial, and the remainder
represent new mutations.
Dystrophin is a cytoplasmic protein located adjacent to the sarcolemmal
membrane in myocytes, it concentrated at the plasma membrane over Z-bands,
where it forms a strong mechanical link to cytoplasmic actin.
dystrophin and the dystrophin-associated protein complex form an interface
between the intracellular contractile apparatus and the extracellular connective
tissue matrix  transferring the force of contraction to connective tissue.
The absence of dystrophin myocyte degeneration
Myotonic Dystrophy
1- Inherited as an autosomal dominant trait a\w a CTG trinucleotide
repeat expansion on chromosome 19q13.2–q13.3affect the mRNA for the
dystrophia myotonia protein kinase (DMPK) sustained involuntary
contraction of a group of muscles & stiffness.
a. Discuss the muscular dystrophies.
Morphology- DMS, BMS
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1) Variation in fiber size (diameter)
(2) Increased numbers of internalized nuclei (beyond the normal
range of 3% to 5%).
(3) Degeneration, necrosis, and phagocytosis of muscle fibers.
(4) Regeneration of muscle fibers.
(5) Proliferation of endomysial connective tissue.
(6) Mytonic dystrophy-MS: (1-5)+ the ring fiber, with a
subsarcolemmal band of cytoplasm that appears distinct from
the center of the fiber (+\-) irregular mass of sarcoplasm
(sarcoplasmic mass)+ relative atrophy of type 1 fibers (IHC)
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in advanced cases muscle fibers undergo degeneration and are
replaced by fibrofatty tissue and collagen.
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In some types od MS , heart muscle and other involuntary muscle and
other organs are affected.
NORMAL DYS-1 test
NEGATIVE DYS-1 test
Mytonic dystrophy
Fiber size variation- Internal nuclei in some fibers- Pyknotic
nuclear clumps
Esterase
NADH stain
a. Discuss the muscular dystrophies.
Clinical features
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a. Discuss the muscular dystrophies.
Clinical features
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Muscular Dystrophy- clinical features
Type
Onset Age (years)
Clinical Features
Other organ systems
involved
Duchenne
Before 5
1.Progressive weakness
of girdle muscles.
2.unable to walk after
age 12
3.progressive
kyphoscoliosis
4.Respiratory failure in
2dor 3d decade.
Cardiomyopathy
Mental impairment
Becker
5-25yr
early childhood to
adult
1.Progressive weakness
of girdle muscles
2. able to walk after
age 15.
1.3. respiratory failure
may develop by 4th
grade
Cardiomyopathy
Emery-Dreifuss
Childhood to adult
Elbow contractures,
humeral and perineal
weakness
Cardiomyopathy
Limb-Girdle
early childhood to
adult
Slow progressive
weakness of shoulder and
hip girdle muscles
Cardiomyopathy
Muscular dystrophy – clinical features
Type
Onset Age
(years)
Clinical Features
Other organ systems
involved
Congenital
At birth or
within 1st few
months
.Hypotonia, contractures,
delayed milestones
Progression to
respiratory failure in
some;
CNS and
Eye abnormalities
Facioscapulohumer
al
Before age 20
Slowly progressive
weakness of face,
shoulder girdle, and foot
dorsiflexion
Deafness
Coat’s (eye) disease
Oculopharyngeal
5th to 6th
decade
Slowly progressive
weakness of extraocular,
pharyngeal, and limb
muscles
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Myotonic
Usually 2nd
decade
May be infancy
if mother
affected
Slowly progressive
weakness of face,
shoulder girdle, and foot
dorsiflexion
Cardiac conduction
defects
Mental impairment
Cataracts
Frontal baldness
Gonadal atrophy
• Ultrasonography- high frequency sound waves.
• Muscle biopsy- histopathology with application of others specific
test, dystrophin and other special test.
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In the affected families females are carriers; clinically asymptomatic but often
have elevated serum CK and show minimal histologic abnormalities on muscle
biopsy.
• Genetic “blood” test- looking for the portion of dystrophic gene
e.g. Duchenne , Becker’s MS
1- Duchenne MD- Corticosteroid- prednisolone (improve muscle strength and delay
progression)
2- Mytonic MD- Phenytoin, Carbamazepine, quinine (treat delayed muscle relaxation)
b. Discuss the disease of neuromuscular junctions.
Definition
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Myasthenia Gravis - MG
is a muscle disease caused by immune-mediated loss of
acetylcholine receptor.
Prevalence: of about 30 in 100,000 persons.
Age: < 40 yrs of life.
Sex: commonly affect female> male, in older equally.
Evidence based nearly all cases: decrease in the number of
muscle acetylcholine receptors (AChRs), and circulating
antibodies to the AChR are present in nearly all cases.
Risk- thymic abnormalities are common in these patients
b. Discuss the disease of neuromuscular junctions.
PATHOGENESIS
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Autoimmune basis:
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Autoantibodies against the AChR lead to loss of functional
AChRs at the neuromuscular junction by:
(1) Fixing complement and causing direct injury to the
postsynaptic membrane.
(2) Increasing the internalization and degradation of the
receptors.
(3) Inhibiting binding of acetylcholine.
Outcomes:
A) Electrophysiologic studies are notable for diminished.
B) Sensory as well as autonomic functions are not affected.
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b. Discuss the disease of neuromuscular junctions.
Morphology
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1- Muscle biopsy- (light microscopic):
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a) Specimens are usually unrevealing.
b) In severe cases type 2 fiber atrophy due to disuse may be found.
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2- Electron microscopy:
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a) The postsynaptic membrane is simplified, and there is loss of
AChRs from the region of the synapse.
b) Immune complexes and the complement membrane attack
complex (C5–C9) can be found along the postsynaptic membrane as
well.
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3- administration of anticholinesterase agents- Test
b. Discuss the disease of neuromuscular junctions.
Clinical features
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1- Weakness begins with the extraocular muscles;
drooping eyelids (ptosis) and double vision (diplopia).
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2- Generalized weakness- the weakness fluctuates over
days, hours, or even minutes.
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3- Intercurrent medical conditions
can lead to exacerbations.
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4- Respiratory compromise
(major cause of mortality)
b. Discuss the disease of neuromuscular junctions.
Management
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1- Better ventilatory support.
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2- Anticholinesterase drugs.
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3- Steroid- prednisone.
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4- Plasmapheresis.
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5- Thymectomy when thymic lesions are present.