histology of nerve and muscle in health and disease

Question 1

connective tissue of skeletal muscle

Answer 1

o Epimysium
o Perimysium
o Endomysium

Question 2

what are myofibres arranged into

Answer 2

fascicles

Question 3

describe the basement membrane of skeletal muscle

Answer 3

o Surrounds individual myofibres
o Collagen, glycoproteins and proteoglycans
o Roles in tensile strength, regeneration, development

Question 4

what happens at the myotendinous junction

Answer 4

o Transmits force of muscle contraction to the tendon

Question 5

innervation of skeletal muscle

Answer 5

• Each fibre innervated by one nerve, with cell bodies in anterior horn of spinal cord or brainstem – lower motor neurone
• One neuron innervates multiple muscle fibres – motor unit
• Neuromuscular junction
o Synapse – rapid transmission of depolarising impulse
o Acetyl choline – binds post-synaptic AChR
• Proprioception
o Muscle spindles – encapsulated intrafusal fibres. Mediate stretch reflexes and proprioception
o Golgi tendon organs - tension

Question 6

sites of pathology affecting muscle and nerve

Answer 6

motor neurone disorders
peripheral neuropathies
neuromuscular transmission defects
primary muscle disease

Question 7

what does enzyme histochemistry reveal

Answer 7

different fibre types

Question 8

muscle fibre types

Answer 8

• Slow twitch (red fibres) – type 1, oxidative, fatigue resistant
• Fast twitch – fatigue rapidly but generate a large peak of muscle tension
o 2A – glycolytic and oxidative (intermediate)
o 2B – glycolytic (white)

Question 9

motor unit

Answer 9

• Motor neuron (lower) and the fibres it innervates
• Neuron and its fibres of same type
• Fibre type dependent on neuron
• Size of motor unit varies between muscles

Question 10

describe how motor units are altered in denervating diseases

Answer 10

• Loss of innervation causes fibre atrophy
• Collateral sprouting from adjacent motor units allows reinnervation – loose fine motor control
• Larger motor units result – this can be detected electrophysiologically
• Conversion of fibres results in fibre type grouping

Question 11

sliding filament theory

Answer 11

• Myosin heads bind actin
• Hydrolysis of ATP provides energy for a conformational change of the myosin head, pulling the actin
• Sarcomeric shortening due to sliding of the filaments NOT change in length of either actin or myosin
• Initiated by increased cytosolic Ca2+

Question 12

requirement of energy for muscle contraction

Answer 12

• High energy requirement from ATP
• Creatine phosphate a short term energy store
• CP replenished by creatine kinase (CK)
• CK is released on muscle fibre damage
• Measurement of serum CK clinically useful

Question 13

mitochondrial cytopathies

Answer 13

• Mitochondrial DNA - Circular ds DNA, Maternally inherited
• Diverse clinical presentations with an emphasis on CNS E.g. MERRF, MELAS, CPEO
• Mutations in either mitochondrial or nuclear DNA
• Mitochondrial mutations – maternal inheritance
• Heteroplasmy - presence of more than one type of organellar genome (mitochondrial DNA or plastid DNA) within a cell or individual →↑mutant load

Question 14

example of mitochondrial cytopathy

Answer 14

Mitochondrial cytopathies affect muscle, so can be diagnosed by muscle biopsy
Ragged red fibres
• Electron transport chain deficits – cytochrome oxidase negative fibres
• Abnormal mitochondrial morphology
• Gene defects

Question 15

proteins involved in membrane stability

Answer 15

merosin, dystroglycans, sarcoglycans, dystrophin, actin

Question 16

what are dystrophies

Answer 16

genetically determined, destructive and mainly progressive disorders of muscle

Question 17

dystrophin

Answer 17

• A large protein encoded by a 2.4 million bp gene on Xp21
• Confers stability to the muscle cell membrane
• Deletion resulting in disruption of the reading frame results in Duchenne
• In Becker’s, and in-frame deletion results in a truncated product

Question 18

neuromuscular transmission

Answer 18

• Nerve impulse results in the release of acetyl choline from synaptic vesicles
• ACh binds to its receptor
• Cation entry results in depolarisation, the end-plate potential
• An action potential travels across the muscle cell membrane and into the T-tubule system
• Calcium is released from the sarcoplasmic reticulum leading to activation of contraction
• Dissociated ACh is hydrolysed by acetyl cholinesterase in the NMJ

Question 19

example of a disorder of neuromuscular transmission

Answer 19

Myasthenia gravis – variable weakness, progressive with sustained effort, eye signs – ptosis
• Autoimmune disease
• Anti-AChR antibodies resulting in a reduction in ACh receptors
• Acetyl cholinesterase inhibitors can improve muscle function

Question 20

myelinated fibre

Answer 20

• In the PNS, the Schwann cell is responsible for the myelin sheath
• Each Schwann cell is responsible for one segment of myelin
• Nodes of Ranvier lie between adjacent myelin segments
• The node is where depolarisation of the membrane occurs
• Myelination allows saltatory conduction

Question 21

peripheral neuropathies

Answer 21

• Damage to motor or sensory neurons – neuronopathies
• Damage to axons – axonopathies
• Selective damage to myelin sheaths - demyelination

Question 22

Axonal degeneration / regeneration – Wallerian degeneration

Answer 22

• Injury to axon – distal fragmentation
• Globules of myelin and axon debris form, initially within Schwann cell
• Axonal sprouts form from proximal part of damaged axon and grow along columns of proliferating Schwann cells
• Regenerated axons can remyelinate

Question 23

demyelination

Answer 23

• Injuries primarily to Schwann cell or myelin sheath
• Demyelination segmental
• Remyelination begins with a thin myelin sheath
• Demyelination results in functional impairment with slowing of conduction velocity