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
Why is prednisolone used for MG?
-leads to remission and marked improvement in 70% of patients with OCULAR and generalized weakness
Why is azathioprine used for MG?
- It’s an immunosuppressant, dampening the prodn of Abs by the immune system
Primary causes of death by MG? (2)
- respiratory failure (in the elderly)
- aspiration pneumonia
What are the different types of muscle fibres? (3)
TYPE I- slow oxidative
TYPE IIa- fast oxidative (aerobic metabolism)
TYPE IIb- fast glycolytic
Which muscle fibre type is easily fatigued?
type IIb
What are fasciculations and what precipitates it?
- visible, fast and spontaneous TWITCH
- seen in healthy muscleswith stress, caffeine, fatigue
Why do fasciculations occurs?
- when a denervated muscle becomes hyperexcitable
- occurs as a sign of motor neurone disease, not MUSCLE.
Define myotonia.
- the delayed relaxation/sustained contraction of the muscle
- hard to stop one shaking their hands
State 4 signs of muscle disease.
- muscle wasting
- hyporeflexia,
- muscle WEAKENING
- myalgia
When may myotonia occur?
- usually hereditary
- involves chloride channels
Name 2 immun-mediated musclular d/os?
POLYMYOSITIS
DERMATOMYOSITIS
How does polymyositis present as? (3)
- symmetrical
- progressive, PROXIMAL weakness
- develops over weeks to months
What is serum finding of Polymyositis?
- raised CK
- responds to Steroid
How is Dermatomyositis different?
- clinically similar but a/w skin lesions
- “heliotrope rash” on face (red rash on swollen eyelids)
- —50% have underlying MALIGNANCY
What is Inclusion Body Myositis?
- degenerative muscle condition
- progressive weakness in 6th decade of life
- thumb is spared
- relentless Muscle wasting
What is the commonest muscular dystrophy? What genetic anomaly results in this?
- MYOTONIC DYSTROPHY
- —autosomal dominant ; trinucleotide repeat d.o
- —> multisystem involvement
How does myotonic dystrophy present as?
- myotonia, weakness, ptosis, frontal balding, cardiac defects
What are muscular dystrophies? (3)
- INHERITED
- NON-inflammatory (unlike myositis)
- no central or peripheral nerve problem
Name 2 muscular dystrophies.
- Duchenne
- BECKER Muscular dystrophy
Name 3 infective causes of muscular d.o..
- coxsacchie
- Trypanosomiasis Cistercercosis (pork)
- borrelia
What is rhabdomyolysis?
- dissolution of muscle
- damage to the skeletal muscle >leakage of large quantities of toxic intracellular contents in to plasma . occurs w/ CRUSH injuries, toxins, post convulsions, extreme exercise
What is the triad of rhabdomyolysis?
- myalgia, muscle weakness, myoglobinuria
- Acute renal failure (reduced urine and dark red urine) and DIC
What are the first few signs of Myasthenia Gravis?
- ocular conditions
diplopia and ptosis
Name causes of NMJ disruption.
- Mysathenia Gravis- Abs to the Ach-R in POST-synaptic cleft
- LAMBERT-EATON $- Abs to the voltage-gated calcium channels
- ORGANOPHOSPHATE poisoning- inhibition to ACh-E
Drugs that may cause symmetrical, often proximal muscular weakness.
- illicit drugs (COCAINE, Heroine)
- alcohol
- corticosteroids
- others: HMG-CoA Reductase, ziduvodine, colchicine, penicillinamine, anti-malarial drugs, contraceptives, diuretics
What are some medical (and cosmetic) uses of botulinum toxin? -
- muscle dystonia
- dysphonia
- SWEATING
- muscle TWITCHING around the eyes
What autoimmune conditions is Myasthenia Gravis a.w?
- DM
- thyroid d.o
- pernicious anemia
- rheumatoid
- SLE
