NMJ d/o Flashcards
What are the skeletal fibres innervated by?
by motor neurones, whose cell bodies reside in the VENTRAL horn of the spinal cord
What is a motor end plate?
it is the synapse between the motor neurones and muscle
What occurs when the AP reaches the axon terminale?
- AP moves along the nerve
- voltage-gated Calcium channels open up, allowing the INFLUX of Calcium ions into the axone terminale
- triggering the release of Ach in to the synaptic cleft from the vesicles
WHat occurs with the release of ACh into the synaptic cleft?
Acetylcholine binds to the Ach-receptor
- opening up Na+/K+ channels
- depolarization starts an AP at the motor end plate
What is the role of Acetylcholinesterase?
- breaks down ACh into acetyl and choline
- choline will then be sequestered into vesicles in the pre-synaptic neurone
What is Curare?
- aka T-tubocurarine
- it blocks depolarization of the post-synaptic neurone by binding to the ACh-R and INHIBITING the binding of ACh
- causes death by RESPIRATORY ARREST as no muscle contraction occurs
Name a pre-synaptic disorder.
Botulism
- by Clostridium Botulinum (present in the SOIL)
- seen in IV drug users (black tar heroin)
How does Cl.Botulinum bring about its action?
- it cleaves the presynaptic proteins involved in Vesicle formation
- blocking vesicle docking (preventing REUPTAKE of CHOLINE)
- no more release of ACH > paralysis of the muscle fibre
How does Botulism present as?
-rapid weakness over 6 hrs (NO SENSORY loss)
What occurs in Lambert Eaton Myasthenic Syndrome (LEMS)?
- Anti-bodies to presynaptic calcium channels leads to LESS vesicle release.
What is LEMS a/w?
- underlying small cell lung carcinoma
How to rx LEMS?
3-4 diaminopyridine
Amifampridine
What is the most common D/O of the neuromusclular jxn? What brings about this condition?
-Myasthenia Gravis - an autoimmune condition with Antibodies to AChR
>reduces no. of FUNCTIONING receptors leading to FATIGUABILITY and WEAKNESS
What are the signs of M.G?
- ptosis
- rapid onset of respiratory d.o
- lower back weakness
- appears sad (B/L facial weakness)
When may the symptoms of Myasthenia Gravis begin to show?
- when ACh receptors reduce to 30% of normal
- –reduced AChR may FLATTEN endplate folds
State the issues brought out by the ACh-Abs? (3)
- blocks Ach from binding to its receptors
- reduces the no. of FUNCTIONING Ach-R
- inflammatory cascade is brought on to the folds of the end plates; flattening it out
What specific gland is said to play a role in MG?
- the thymus
- 75% have thyoma or Hyperplasia
When is the usual onset of Myasthenia Gravis in Males and Females?
- M: 60s or 70s
- F: 30s
F:M= 3:2
What is the pattern of weakness like in pts with MG?
- FLUCTUATING
- worse at the END of the day
What is most common presentation of MG?
- EXTRAocular weakness, facial and bulbar weakness
- PROXIMAL limb weakness
Why do MG pts lose weight?
- as they get tired of chewing
- thus won’t be eating as much
What is Myasthenic Crisis?
- complication of MG
- worsening of the condition results in respiratory failure
- requiring mechanical intubation and ventilation
What acute treatment is given for MG?
- acetylcholine-esterase INHIBITOR (pyridostigmine)
- IV Immunoglobulin
- THYMECTOMY (even w.o abnormality)
If symptomatic rx does
not work for MG…?
- steroids (PREDNISOLONE or steroid sparing agents –AZATHIOPRINE/MYCOPLENOLATE
- plasma exchange/immunoglobulin
