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Flashcards in Diseases of muscle Deck (29):

What are the muscle fibre components?

- Basal Lamina
- Plasma membrane
- Mitochondria
- Sarcoplasmic reticulum
- Myofibrils
- Myonuclei


What functional systems are involved in control of muscle?

- Ion fluxes
- Neuromuscular transmission
- Excitation-contraction coupling
- Oxidative phosphorylation
- mRNA transport


What symptoms might you see in muscle disease?



What clinical investigations are used in muscle disease?

- Clinical examination (neurological)
- Electromyograph
- Nerve conductions studies
- Serum/Blood investigations


What is dystrophin?

Links the ECM with the actin cytoskeleton.


How might muscle disease be classified biologically?

Neurogenic muscle disease - problem with the nerve/spine/brain

Motor end-plate disorders

Primary muscle diseases - myopathies (destructive and non-destructive)


What is the basal lamina?

- Links muscle fibres to endomyseal connective tissue
- Survives muscle fibre necrosis
- Acts as a platform for satellite cell proliferation


Which proteins may be deficient in dominant limb girdle muscular dystrophy?

- Lamin A/C
- Caveolin 3


Which proteins may be deficient in recessive limb girdle muscular dystrophy?

- Calpain 3
- Dysferlin
- a,b,g,d - sarcoglycan


Which proteins may be deficient in X-linked limb girdle muscular dystrophy?

- Dystrophin (Duchenne, Becker)
- Emerin (Emery Dreifuss)


What is Duchenne Muscular dystrophy?

- Sex-linked recessive disorder
- Gene product - dystrophin
- Relentlessly progressive wasting
- Chair-bound by 12 years
- Proximal muscle weakness
- Hypertrophy of calves


What are diseases of myonuclear abnormalities?

Defects of nuclear membrane-related proteins (emerins, lamin A/C)
- Limb girdle muscular dystrophy 1B
- Emery-Dreifuss Muscular Dystrophy

Centronuclear myopathies
- Myotubular myopathy


What is Emery-Dreifus muscular dystrophy?

- X-linked recessive
- Weakness of proximal arm and distal leg muscles
- Early contractures
- Cardiomyopathy


What investigations are neccessary in limb-girdle musclular dystrophy and why?

- Phenotypic overlap with spinal muscular atrophy and BMD
- Histochemistry inadequate investigation
- Need immunohistochemistry to exclude BMD and SMA


What is central core disease?

- Not usually detected until child has started walking
- Dominantly inherited
- The central core is a well demarkated zone in the centre of a muscle fibre, devoid of normal histochemical reactivity (NADH-Tr)
- Cores only occur in type I fibres


What is nemaline myopathy?

- Present with generalised neonatal hypotonia
- Respiratory insufficiency
- High arched palate
- Kyphoscoliosis
- Autosomal recessive


What is malignant hypothermia?

- Abnormal susceptibility to certain inhalational anaesthetic agents
- Prolonged rise in intracellular calcium ions
- Rigid contractions and elevation in body temperature
- Muscle biopsy changes mild & non-specific


What is myotonic dystrophy?

- Dominantly inherited
- Myotonia and progressive weakness of facial muscles
- Onset 20-30 years
- Cardiac conduction defects


What is the typical histopathology of myotonic dystrophy?

- Selective atrophy of type I fibres
- Type II hypertrophy
- Paucity of type IIb fibres
- Central nuclei are an early feature
- Motheaten & targetoid fibres
- Ring fibres common


What is facioscapulohumeral dystrophy?

- Dominantly inherited disorder
- Also affects myocardium
- Presents early in adult life
- Associated with progressive deafness
- Retinal vasculopathy


What is the histology of facioscapulohumeral dystrophy?

- Histological changes may be minimal
- Scattered angular atrophic fibres
- Little else is specific
- Biopsy an affected muscle (Biceps or triceps) - Deltoid often preserved


What are the disorders of catabolic metabolism?

Lysosomal disorders
- Alpha glucosidase deficiency syndrome
- LAMP-2 deficiency
- X-linked myopathy with excessive autophagy

Proteolytic disturbances
- Calpain 3 deficiency


What are the neurogenic muscle diseases

- Motor neuron disease (MND)
- Spinal muscular atrophy (SMA)
- Hereditary motor and sensory neuropathies (HMSN)


What is myasthenia gravis?

- Autoimmune disease with antibodies, usually IgG, against the acetylcholine receptor
- Muscle biopsy NOT an appropriate diagnostic test
- See mild changes of denervation atrophy


What is Eaton-Lambert Myasthenic syndrome?

- Rare non-metastatic manifestation of malignancy, usually oat-cell carcinoma of the bronchus
- No specific changes in the muscle biopsy


What is mitochondrial myopathy?

- Ragged red fibres
- EM reveals these to represent whorled cristae or crystalline inclusions
- Accumulation of lipid on Oil Red O stain
- Biopsy may be relatively normal


What is dermatomyositis?

- Inflammatory myopathy responsible for chronic debilitating disease
- Associated with a scaly rash
- Mononuclear cell infiltration of muscle with fibre necrosis and replacement fibrosis
- Inflammation predominantly perimysial where B cells predominate
- In endomysium T4 cells predominate
- MAC-deposition (C5-9) can be detected by IHC indicating that the humoral antibody-dependent mechanism is mediated by complement


Give examples of drug-induced myopathies.

- Statin myopathy
- Steroid induced myopathy probably most common.
--Type II fibre atrophy
--Increase in lipid droplets
- Most severe drug reaction is an acute necrotising myopathy causing rhabdomyolysis, myoglobinuria & renal failure


What is motor neuron disease?

- Characterised by widespread degeneration of motor neurons
- Involves anterior horn cells, brain stem nuclei and Betz cells
- Upper & lower motor neuron signs with wasting associated with spasticity & brisk reflexes

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