Disorders of Neuromuscular Transmission Flashcards
Acquired Neuromuscular Disorders:
– Myasthenia Gravis
– Lambert-Eaton Myasthenic Syndrome
– Botulism
– Organophosphate Poisoning
Heritable Neuromuscular Transmission:
– Congenital Myasthenic Syndromes
What is needed for NMJ release?
Calcium
First steps in NMT:
- Action potential arrives at motor terminal
- Voltage-gate Ca++ channels open-
Ca++enters - Ach vesicles migrate and fuse
- Ach is released into the synaptic cleft
Last steps in NMT:
- Ach binds to Ach Receptor and Na+ enters
- End-Plate Potential is generated
- Sarcolemma depolarizes at EPP threshold
- Ach is degraded by Acetylcholinesterase
Pre-synaptic disorders:
– Eaton-Lambert Syndrome
– Botulism
– Congenital Deficiency Ach synthesis
Synaptic disorder:
Organophosphate poisoning
Post synaptic disorders:
– Myasthenia Gravis
– Congenital
* Abnormal AChR
Amount of Ach of each synaptic vesicle
Quantum
Total number of quanta release/ action potential
Quantal content
Autoimmune disease of the
neuromuscular junction
Myasthenia gravis
Can be associated with other autoimmune disorders and neoplasms (Thymoma)
Myasthenia gravis
Pathophysiology of Myasthenia gravis:
- Antibodies directed against the acetylcholine receptor or other closely- associated proteins
- Cross-linking or blocking of receptor
- Complement-mediated destruction of end- plate
Characterized by: droopy eyes (ptosis), double vision, nasal voice in afternoons, diffuse weakness, resiratory muscle involvement
Myasthenia gravis
What is the simpson test used for?
Ptosis - myasthenia gravis
Tests used for MG:
1.Tensilon test
2.Anti Ach R serum antibody
3.Anti Muscle Kinase
4.Anti thymoma
5.EMG
What is Tensilon test?
Short-acting Acetylcholinestherase inhibitor (increases Acetylcholine)
Which NMJ disease causes: Autoantibodies to pre-synaptic voltage gated calcium channels (motor nerve terminal)
Impairment of quantal release of Ach
Lambert Eaton Myasthenic Syndrome (LEMS)
Characterized by:
- Weakness in proximal> distal muscles
- Proximal legs > arms
- Improved strength with brief-exercise
- Diminished or absent deep tendon reflexes
- Autonomic symptoms: dry mouth, blurred vision, impotence
LEMS
Pre-synaptic block of acetylcholine release through cleavage of excitosis proteins (SNARE)
Botulism
Three major presentations of botulism:
– Classic (Food-Borne)
– Infant Botulism
– Wound Botulism (IV drug injection)
Characterized by:
18-38 hr incubation, diffuse weakness starting from eyes to limbs, reduced tendon reflex, dilated pupils, blured vision, GI problems
Botulism
Dozen D’s
Botulism
Accidental Poisoning with Insecticides and Nerve Gas (Sarin, Soman, Tabun)
Organophosphate toxicity
Excess Acetylcholine Diseases = Constant Depolarization
Organophosphate toxicity
Inihibition of Endogenous Acetylcholinesterase
SLUDGE
salivation
lacrimation
urination
diarrhea
gi
emesis
DUMBELS
diarrhea
urination
miosis
bronchospasm
emesis
lacrimation
salivation
Heterogeneous genetic disorders of neuromuscular transmission
Congenital Myasthenic Syndromes
Most common- mutations in post-synaptic and synaptic proteins
*Onset in childhood
Congenital Myasthenic Syndromes
Can be associated with neoplasms:
Thymoma
(MG) or Small Cell Lung CA (LEMS)
Can be associated with toxins:
Botulism and Organophosphates
