histology of nerve and muscle in health and disease Flashcards
connective tissue of skeletal muscle
o Epimysium
o Perimysium
o Endomysium
what are myofibres arranged into
fascicles
describe the basement membrane of skeletal muscle
o Surrounds individual myofibres
o Collagen, glycoproteins and proteoglycans
o Roles in tensile strength, regeneration, development
what happens at the myotendinous junction
o Transmits force of muscle contraction to the tendon
innervation of skeletal muscle
• 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
sites of pathology affecting muscle and nerve
motor neurone disorders
peripheral neuropathies
neuromuscular transmission defects
primary muscle disease
what does enzyme histochemistry reveal
different fibre types
muscle fibre types
• 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)
motor unit
- 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
describe how motor units are altered in denervating diseases
- 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
sliding filament theory
- 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+
requirement of energy for muscle contraction
- 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
mitochondrial cytopathies
- 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
example of mitochondrial cytopathy
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
proteins involved in membrane stability
merosin, dystroglycans, sarcoglycans, dystrophin, actin
what are dystrophies
genetically determined, destructive and mainly progressive disorders of muscle
dystrophin
- 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
neuromuscular transmission
- 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
example of a disorder of neuromuscular transmission
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
myelinated fibre
- 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
peripheral neuropathies
- Damage to motor or sensory neurons – neuronopathies
- Damage to axons – axonopathies
- Selective damage to myelin sheaths - demyelination
Axonal degeneration / regeneration – Wallerian degeneration
- 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
demyelination
- 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
