Week 4 Flashcards

1
Q

What does a motor unit comprise of

A

A a-motoneuron
All extrafusal skeletal muscle fibres it supplies

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2
Q

What is the a-motoneurone

A

A specific subset of neurones of the nervous system through which all commands from the brain are relayed to skeletal muscles

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3
Q

What is a neuromuscular junction

A

The site of communication between the motoneurone and muscle

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4
Q

Theres 2 variants to the classification of motoneurone

A

Upper and lower motoneurones
Arranged strictly in series, damage to either of these leads to motoneurone signs

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5
Q

Where are upper motoneurones found

A

Reside in the brain in the cerebral cortex and travel down to the brain stem or spinal cord

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6
Q

Where are lower motoneurons’ cell bodies found

A

In the ventral horn of spinal cord grey matter or cranial nerve motor nuclei in the brain stem

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7
Q

What is meant by innervation

A

The term used to describe the normal state of nerve supply to a muscle of other target
Act of stimulating

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8
Q

Denervation

A

Depriving muscle of its nerve supply

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9
Q

Re-innervation

A

Re-growth of the nerve to re-supply the muscle
Re-innervation of the original effector organ is not always successful, most nerves reinnervate an effector organ that is different from its original target
This leads to emergence of all sorts of unexpected results

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10
Q

What leads to death of motoneurones

A

Loss or damage to the motoneurones cell body
Theres a class of diseases that target cell bodies of motoneurones
This would result in the denervation of muscles

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11
Q

What is poliomyelitis

A

Communicable infection that targets cell bodies of lower motoneurones of body
Also known as infantile paralysis
Caused by infection by polio virus
Leads to toxic infection of cell bodies of neurones of ventral horn
Any motoneurones of spinal cord are susceptible to virus

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12
Q

What does death of motoneurones lead to

A

Denervation hence paralysis of muscles they supply
Toxic infection of cell bodies of neurones of ventral horn can lead to death of dorsal horn too

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13
Q

What is motoneuron disease

A

Rare condition affecting brain and nerves
2 variants
Disease simultaneously kills both lower and upper motoneurones. Known as progressive supranuclear palsy
The disease targets only lower motoneurone

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14
Q

What is programmed cell death known as

A

Apoptosis

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15
Q

Which motoneurones dont undergo apoptosis under MD

A

Motoneurones supplying extraocular muscles
Motoneurones supplying anal sphincter

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16
Q

Implications of disorders of motoneurones axon and LMN signs

A

Loss or damage to motoneurones axon doesn’t necessarily lead to death of motoneurone
However it leads to the removal innervation to muscle- known as denervation

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17
Q

Complete transaction of axons of motor nerve

A

Exemplified by crushing injuries to limbs, stabbing injuries
Usually accidental
Often inevitable involvement of nerves supplying affected part of body
Results in denervation of muscles involved

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18
Q

What is Guillain-Barré syndrome

A

G-B syndrome is acquired as a complication following a viral infection such as common cold
Rare and serious condition mainly affects feet, hands, limbs causing numbness, weakness and pain

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19
Q

Demyelination of axons of motoneurones

A

Diabetic neuropathy leads to demyelination of axons of both sensory and motor axons
Clinical signs reverse when condition is cured or goes into remission
Clinical motor signs can return with relapse
Vision loss, muscle weakness, muscle stiffness and spasms, loss of coordination, changes in bladder and bowel function, walking problems

20
Q

What is peripheral neuropathy

A

Type of nerve damage that can cause pain, weakness, numbness
Nerves located outside Brian and spinal cord

21
Q

Implications of disorders of neuromuscular junction and LMN signs

A

Neuromuscular junction is necessary element to integrity of motor unit
Theres a class of diseases that target NMJ in its own right
LMN damage include weakness, muscle atrophy (wasting), and fasciculations (muscle twitching), decreased reflexes

22
Q

What is the NMJ

A

It’s the tissue interface between motoneurone and muscle
It’s synaptic interface
Special synapse
Also called end plate

23
Q

How does NMJ work

A

Motoneuron forms presynaptic membrane, releases acetylcholine as neurotransmitter
The muscle forms post synaptic membrane, expresses Nicotinic receptors that convert chemical messages carried by Ach
The synaptic cleft expresses enzyme acetylcholine esterase that destroys any Ach that isn’t bound to postsynaptic membrane

24
Q

What does botulinum toxin do

A

Acts to deplete the presynaptic terminal of NMJ of its neurotransmitter
Effect of botulinum toxin is dry mouth and difficulty swallowing

25
Q

What is myasthenia gravis

A

Rare genetic disease of neuromuscular junction
Nicotinic receptors of postsynaptic membrane of NMJ are selectively destroyed by persons immune system, blocked by antibodies. Reduced transmission of ACh, symptoms worsen then get better when rest
It affects any neuromuscular junction of body in affected individuals. Not localised
Droopy eyelids, Ptosis
Ophthalmoplegia- weakness or paralysis of eye muscles
Brings about flaccid weakness of affected muscles. Fatigability, proximal weakness
Can cause respiratory failure if muscle of respiration affected

26
Q

Duchenne muscular dystrophy- genetic disorder

A

Genetic
Progressive muscle weakness
Defects in muscle proteins
Death of muscle tissue
Eventual death of affected individual

27
Q

Lower motoneuron signs

A

Lesions of lower mn lead to characteristic impairments of movements
Theres a series of emergent clinical presenting signs known as LMN signs
LMN signs are very different from upn signs

28
Q

Why are NMJ specialised for rapid transmission

A

Lots of places where the neurotransmitter is released
Lots of active zones where vesicles release contents
More than other synapses in CNS
Contain junctional folds which contain postsynaptic densities

29
Q

Role of Ca2+ in excitation-contraction coupling

A

Calcium conc greater outside- concentration gradient
Action potential in post synaptic terminal
Depolarisation opens voltage gated calcium channels, Ca enters presynaptic terminal
So intracellular conc increases
Fusion of vesicles with presynaptic membrane, neurotransmitter (ACh) released

30
Q

Ca2+ induced vesicle fusion

A

Calcium entry into presynaptic terminal triggers vesicle fusion
Calcium sensor is synaptotagmin (calcium binds to this and it changes shape)
Change in conformation on ca binding triggers vesicle fusion
Exocytosis of neurotransmitter
Exact mechanism is unclear

31
Q

ACh transmitter end plate

A

ACh binds to Nicotinic ACh receptors on postsynaptic end plate membrane
2 molecules of ACh needed to bind
Ionotropic receptor/ ligand gated ion channel

32
Q

NMJ- specialised synapse

A

Presynaptic- multiple quanta release- many vesicles releasing contents in CNS single vesicle only
Postsynaptic- junctional folds, high density of nACh receptors ( allow sodium in end plate potential), high density of voltage gated Na+ channels- action potential, end plate potential

33
Q

Why is End plate potential so high

A

So many receptors activated by so much neurotransmitter
Large depolarisation

34
Q

ACh transmitter at end plate

A

ACh binds to nACh receptors
Channel opens-permeable to Na+ and K+
Em muscle cell= -90mV
Na+ influx»> K+ efflux because Em«Ena whereas Em~Ek
Large driving force for sodium
EPP= -20Mv

35
Q

How does the end plate potential work

A

EPP initiates an AP in muscle, not action potential itself
EPP decays as it moves away from end plate- Nicotinic receptors not expressed anywhere else other than end plate
AP then travels through muscle cell

36
Q

Properties of EPP

A

Timing presynaptic AP to EPP ~1msec
EPP generated by ligand gated channels
Very large in comparison to most synaptic potentials- ,many ACh vesicles, high density of nAChRs
Threshold for AP generation easily passed- high density Na+ voltage gated channels at end plate

37
Q

The postsynaptic action potential

A

AP invades T tubules system
Allows transmission of AP deep into muscle fibre to separate myofibrils
Propagate along muscle fibre

38
Q

Where is calcium ions released from

A

Sarcoplasmic reticulum

39
Q

Fate of ACh

A

ACh binds to nAChR for ~ 1ms
Released into synaptic cleft- hydrolysed by acetylcholinesterase AChE
Concentration ACh decreased rapidly
Choline taken back up to make new ACh
Choline acetyl transferase catalyses synthesis ACh in cholinergic neurones

40
Q

Myesthenia gravis

A

Autoimmune disease which affects expression of receptors so synapse fails. Not enough nAChRs postsynaptically to get reliable transmission at this synapse which should never fail
Caused by failure of NMJ
Do not get large enough EPP to generate AP
Muscle weakness during sustained activity

41
Q

What muscles first affected in myesthenia gravis

A

Skeletal muscle of the eye fatigue most quickly so symptoms seen here first
Eyes most active muscles in body

42
Q

Treatment of myesthenia gravis

A

AChE inhibitors
-prolongs signal
-neostigmine-acetylcholinesterase inhibitor
Allows ACh to last longer so receptors can get enough ACh to stimulate them

43
Q

Disorders of the motor unit

A

Death or dysfunction of the muscle gives symptoms similar to lower motoneuron signs
-characteristic impairments of movement
-flaccid muscle weakness
-hypotonia (low level of muscle tone) or atonia (lack of muscle tone)
-hyporeflexia (skeletal muscles have a decreased or absent reflex response) or areflexia (absence of deep tendon reflexes)
-denervation of muscle atrophy
-fasciculations (acute phase)
-muscle wasting

44
Q

Duchenne muscular dystrophy

A

A genetic progressive muscle weakness. Defects in muscle protein dystrophin causes death of muscle tissue

45
Q

UPN signs

A

Weakness
Spasticity- a condition in which there is an abnormal increase in muscle tone or stiffness of muscle, which might interfere with movement speech or be associated with discomfort or pain
Clonus
Hyperflexia

46
Q

Clinical sign that would be seen in acute phase of LMN lesion before muscle atrophy

A

Fasciculations- caused by increased receptor concentration on muscles to compensate for lack of innervation

47
Q

Consequence of denervating a skeletal muscle fibre

A

If a muscle cell is not reinnervated it may ultimately die