Mechanisms of dysfunction of

muscles

Prof. Vajira Weerasinghe

Department of Physiology

Lecture is available at www.slideshare.net/vajira54

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

Site of lesions

Cortex

Internal capsule

Brain stem

Spinal cord

Anterior horn cell

Motor nerve

Neuromuscular junctionMuscle

Motor unit

• A single motor neuron and the group muscle fibres supplied by the branches of the axon

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

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

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

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

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)

Denervation

Normal innervation

Reinnervation

Axonal degeneration

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

Physiological basis of muscle contraction

Muscle contraction

• Excitation - contraction coupling

– Excitation : electrical event– Contraction : mechanical event

THIN FILAMENT (Actin)

THICK FILAMENT (Myosin)

Muscle fibre types

Physiological concepts

slow & fast fibres

• Slow twitch fibre (type I fibre)

• Fast twitch fibre (type II fibre)

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

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

fast slowfibres fibres

Sprinters 63% 37%

Marathon runners 18% 82%

Average man 55% 45%

Muscle dysfunction

• Muscle fatigue

• Muscle cramps

• Muscle strain

• Muscle disorders

Myopathies

• Primary muscle disorders are called myopathies

• eg.– Proximal myopathy– Congenital myopathy– Muscular dystrophy– Myositis

Congenital myopathy (floppy baby)

Congenital myopathy produces floppy baby

Muscular dystrophy

Primary muscle disorder produces gross muscle wasting

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

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

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

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

SMA (spinal muscular atrophy)DSMA (distal spinal muscular atrophy)

MND (motor neuron disease)

Neuromuscular junction disorders

• eg. myasthenia gravis

• Muscle fatiguability

• Ptosis

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

EMG Machine

EMG Needle EMG recording

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

Normal resting

Normal full recruitment

Motor unit action potentials

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

fibrillations

Reduced recruitment

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

Giant motor units

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

Myopathic EMG pattern

EMG recording – myotonia

• Rest:– Prolonged continuous activity– Triggered by needle position or percussion

– “Bomb diver sound”– Myopathic pattern

Myotonia - Bomb diver pattern

Single fibre EMG

• This is a specialised EMG technique

• This is useful to diagnose myasthenia gravis

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