1. Mechanisms of
dysfunction of
muscles
Prof. Vajira Weerasinghe
Department of Physiology
Lecture is available at
www.slideshare.net/vajira54

2. Objectives
1. Recall the physiology of the motor unit and its
neural control
2. Outline how disorders at different levels in the
control mechanisms affect muscle function

3. Site of lesions
Cortex
Internal capsule
Brain stem
Spinal cord
Anterior horn cell
Motor nerve
Neuromuscular junction
Muscle

4. Motor unit
• A single motor neuron and the group muscle
fibres supplied by the branches of the axon

6. motor unit
• muscle contraction occurs in terms of motor
units rather than by single muscle fibres
• a motor unit is defined as
– anterior horn cell
– motor neuron
– muscle fibres supplied by the neuron

7. motor unit
• Innervation ratio
– motor neuron:number of muscle
fibres
• in eye muscles
– 1:23 offers a fine degree of
control, less strength
• in calf muscles
– 1:1000 more strength less
precise control

8. Principle of recruitment of motor units
• Increase in the tension of a muscle is due to
progressive recruitment of motor units
• eg.
– Mild contraction – few motor units are recruited – mild
tension
– Moderate contraction – many motor units are recruited –
moderate tension
– Strong contraction – all the motor units are recruited –
maximum tension

9. The size principle
• Ordered recruitment of motor units arise
because
– Smaller motor units are the easiest to excite
– Smaller motor units have low threshold
• With progressive recruitment of motor units
larger motor units are also recruited

10. Effect of damage to a nerve
• Demyelination
• Denervation
• Axonal degeneration
• Reinnervation
• Regeneration
• Classified as
– Neuropraxia
– (mild damage, no significant axonal degeneration)
– Axonotmesis
– (significant axonal degeneration)
– Neurotmesis
– (complete nerve section)

11. Normal innervation
Denervation
Axonal degeneration
Reinnervation

12. Effect of damage to a nerve
• Denervation occurs
– Features of denervation are the appearance of fibrillations
and reduced recruitment pattern
• After few weeks muscle fibres start spontaneous contractions on
their own called “fibrillations”
• This is due to denervation hypersensitivity
• Recruitment pattern is reduced because many motor units do not
function. Only those remaining motor units will function
• Later reinnervation occurs
– Later remaining motor units will form new branches and
increase their number of muscle fibres therefore with time
reinnervation pattern will result

13. Physiological basis of muscle
contraction

14. Muscle contraction
• Excitation - contraction coupling
– Excitation : electrical event
– Contraction : mechanical event

15. THIN FILAMENT (Actin)
THICK FILAMENT (Myosin)

17. Muscle fibre types
Physiological concepts

18. slow & fast fibres
• Slow twitch fibre (type I fibre)
• Fast twitch fibre (type II fibre)

19. Slow twitch fibre (type I fibre)
– Slow cross-bridge cycling
– slow rate of shortening (eg. soleus muscle in calf)
– high resistance to fatigue
– high myoglobin content
– high capillary density
– many mitochondria
– low glycolytic enzyme content
– They are red muscle fibres

20. Fast twitch fibre (type II fibre)
– rapid cross-bridge cycling,
– rapid rate of shortening (eg. extra-ocular
muscles)
– low resistance to fatigue
– low myoglobin content
– low capillary density
– few mitochondria
– high glycolytic enzyme content
– fast twitch fibers use anaerobic metabolism
to create fuel, they are much better at
generating short bursts of strength or speed
than slow muscles

21. fast slow
fibres fibres
Sprinters 63% 37%
Marathon
runners 18% 82%
Average man 55% 45%

22. Muscle dysfunction
• Muscle fatigue
• Muscle cramps
• Muscle strain
• Muscle disorders

23. Myopathies
• Primary muscle disorders are called
myopathies
• eg.
– Proximal myopathy
– Congenital myopathy
– Muscular dystrophy
– Myositis

24. Congenital myopathy
(floppy baby)
Congenital myopathy produces floppy baby

25. Muscular dystrophy
Primary muscle disorder produces gross muscle wasting

26. Duchenne Muscular dystrophy
• Duchenne muscular
dystrophy is a lethal
degenerative disease of
muscles in which the
protein dystrophin is
absent
• Gower’s sign is seen
• Dystrophic muscles are
more susceptible to
stretch-induced muscle
damage

27. Dystrophin
• Dystrophin is a rod-shaped cytoplasmic protein, and a
vital part of a protein complex that connects the
cytoskeleton of a muscle fiber to the surrounding
extracellular matrix through the cell membrane
• It provides an anchoring function to the muscle
proteins

29. Myotonia
• Some muscle disorders could be due to derangement
of electrical activity in the muscle membrane
– Na+, K+ Cl- channel derangements
– Called channelopathies
– Myotonia dystrophica, myotonia congenita
• Lack of K+ or Cl- channels
• Depolarisation is normal
• Repolarisation will not take place normally

31. Anterior horn cell diseases
• SMA (Spinal muscular atrophy)
• Affect infants
• Poor prognosis
• Several types are present SMA type I, II etc
• DSMA (Distal spinal muscular atrophy)
• Affect adolesecents
• Main feature is a wasting of small muscles of the hand
• Non-progressive and benign
• MND (Motor neuron disease)
or ALS (amyotrophic lateral sclerosis)
• Affect adults (after 40 years)
• Features include weakness and wasting of limb muscles, tongue fasciculations,
dysarthria, dysphagia
• Slowly progressive and poor prognosis

32. DSMA (distal spinal muscular atrophy)
SMA (spinal muscular atrophy)
MND (motor neuron disease)

33. Neuromuscular junction disorders
• eg. myasthenia gravis
• Muscle fatiguability
• Ptosis

34. Electromyography
• This is a neurophysiological test done in order to
detect muscle disorders
• Recording electrodes are needles (EMG needles)
• They contain cathode and anode in the form of a
needle
• This is inserted into the muscle
• Motor unit recording pattern is recorded visually in the
screen and sound pattern is recorded from a
loudspeaker

35. EMG Machine
EMG Needle EMG recording

36. EMG recording - normal
• At rest
– No activity
• Ask the subject to make a voluntary contraction
– Motor unit action potentials amplitude and duration
are calculated
– Recruitment pattern is recorded

37. Normal resting Motor unit action potentials
Normal full recruitment

38. EMG recording – denervation pattern
• At rest
– Fibrillations
• Ask the subject to make a voluntary contraction
– Motor unit action potentials amplitude and duration
normal
– Recruitment pattern is reduced

39. fibrillations
Reduced recruitment

40. EMG recording – denervation with
reinnervation pattern
• At rest
– Fibrillations, fasciculations
• Ask the subject to make a voluntary contraction
– Motor unit action potentials amplitude and duration
increased
• (in motor neuron disease – anterior horn cell disease –
giant motor units are seen)
– Recruitment pattern is reduced

41. Giant motor units

42. EMG recording – myopathic pattern
• At rest
– No activity or fibrillations
• Ask the subject to make a voluntary contraction
– Motor unit action potentials amplitude and duration
are reduced
– Early full recruitment pattern

43. Myopathic EMG pattern

44. EMG recording – myotonia
• Rest:
– Prolonged continuous activity
– Triggered by needle position or percussion
– “Bomb diver sound”
– Myopathic pattern

45. Myotonia - Bomb diver pattern

46. Single fibre EMG
• This is a specialised EMG
technique
• This is useful to diagnose
myasthenia gravis

47. Clinical use of needle EMG
• Investigation of nerve injuries and their recovery
– Denervation pattern
– Reinnervation pattern
• Diagnosis of anterior horn cell diseases
– SMA, DSMA, MND (or ALS)
• Diagnosis of muscle disorders
– Myopathy and myositis
– Muscular dystrophy
– Myotonia dystrophica
• Diagnosis of myasthenia gravis
– Single fibre EMG