MSK Muscle disorders Flashcards
Types of muscle disorder:
- Intrinsic diseases of muscle (myopathies)
a. Genetically determined
b. Acquired - Neurological diseases
- Fatigue or effort syndrome
- Tumours (rare)
Muscular Dystrophies: Characterised by
Progressive muscle weakness, defects in muscle prteins, fibre atrophy, and necrosis of muscle cells
Muscular Dystrophies: Types
9
Muscular Dystrophies: Most common and severe
Duchenne muscular dystrophy (DMD), which involves mutations of dystrophin gene.
Muscular Dystrophies: Becker
Less severe form of DMD
Muscular Dystrophies: Dystrophin
- Forms part of transmembrane “dystrophin – glycoprotein complex” that represents the costamere
- Prevents excessive stress on cell membrane during muscle contraction
- Stabilises sarcolemma and protects muscle fibre from disruption during contraction
- Possible role in regulating calcium levels
Muscular Dystrophies: Lack of Dystrophin in studies showed
• Increases susceptibility to membrane damage and allows excess calcium to penetrate cell membrane
Metabolic Myopathies: Includes disorders of
Glycogen metabolism, lipid metabolism or phosphagen system
Metabolic Myopathies: Cause
Impaired energy supply via affected pathways
Mitochondrial Myopathies: Involves
Structural abnormalities of mitochondria
Mitochondrial Myopathies: Cause
Dysfunction of mitochondrial pathways → impaired aerobic metabolism
Mitochondrial Myopathies: Often linked to
Mutations in mtDNA; mutations of nuclear DNA may cause dysfunction in respiratory chain
Disorders of muscle membranes (channelopathies) Periodic paralysis due to
Inexcitability of muscle that causes temporary paralysis or weakness
Disorders of muscle membranes (channelopathies) Myotonic dystrophy characterised by
Abnormal resting membrane potential
Congenital Myopathies: Definition
Myopathies that are present at birth or begin during infancy
Congenital Myopathies: Transmission
Usually hereditary and progress slowly
Congenital Myopathies: Characterised by
Specific morphologically abnormalities that cause muscle weakness and loss of muscle tone in infancy and delayed motor development during childhood
Diagnosis and investigation of muscle disease:
- DNA analysis
- Muscle biopsy
- Exercise testing
- Electromyography
- Plasma creatine kinase analysis
DNA Analysis:
- Used to investigate disorders with major genetic component
- Single gene disorders (caused by mutation in one gene) are easiest to identify
- Possible to predict gene involved from the aberrant protein (e.g. dystrophin in DMD)
Muscle Biopsy: Enzymes of glycolysis
Stain for enzymes involved in glycolysis e.g. PFK and myophospharylase → used to identify such as myophosphorylase defiency (McArdle’s disease)
Muscle Biopsy: Storage Products
Periodic acid-Schiff Stains for Glycogen
Demonstrates abnormal glycogen storage in patients with glycogenesis
Muscle Biopsy: Enzymes of oxidative metabolism
Oxidative enzymes e.g. NADH, cytochrome C oxidase, SDH used in diagnosis of mitochondrial myopathies
CCO used to demonstrate respiratory chain abnormalities
SDH used as marker enzyme for mito
→ Indicates abnormalities in mit distribution e.g. in mito myopathies, core disease, MD
Ischaemic exercise disease: Used to investigate
Certain metabolic myopathies
Ischaemic exercise disease: Process
- Baseline blood sample taken at rest
- Circulation of forearm occluded whilst subject exercises forearm for fixed time or t o exhaustion
- Circulation restored, blood samples taken immediately after exercise and during recovery
- Blood analysed for lactate and ammonia
Ischaemic exercise disease: Failure to produce lactate
• Disorders of glycogen metabolism e.g. myophosphorylase defiency
Ischaemic exercise disease: Impaired ammonia production indicative
Of myoadenylate deaminase defiency (MADD)
Incremental/steady state exercise test: Aids
Diagnosis/assessment of mito myopathies
Incremental/steady state exercise test: Process
- Baseline blood sample taken at rest
- Subject exercises at series of incremental loads on bicycle ergometer or treadmill
- At each load, blood samples taken for lactate analysis, further samples taken during recovery
Incremental/steady state exercise test: Elevated lactate levels for
Given workload indicates increased conversion of pyruvate to lactate
Electromyography:
- Intramuscular (needle) EMG used to investigate alterations in muscle activity as a result of disease
- Most commonly studied features are:
a. Insertional activity
b. Spontaneous activity
c. MUAP characteristics
d. Recruitment patterns - EMG changes occur as a result of membrane disorders that affect excitability of cell membrane, or as result of marked atrophy or necrosis.
Plasma Creatine kinase analysis:
- Plasma CK levels may rise temporailiy in healthy subjects in healthy subjects following eccentric exercise (as shown in figure)
- Elevated plasma CK levels indicate damage to muscle cell membrane, and are common feature of DMD.
