NMJ and Motor Unit Diseases Flashcards by Nicole Pritchard

What are the two origins of muscle weakness?

Nervous pathway

Muscle itself

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what are the disorders associated with lesions in the SOMA of the motor unit?

Amyotrophic Lateral Sclerosis (ALS)

Poliomyelitis

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what are the disorders associated with lesions in the AXON of the motor unit?

toxins, drugs and axotomy

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what are the disorders associated with lesions in the SCHWANN CELL of the motor unit

Guillain-Barre

Diphteria

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what are the disorders associated with lesions in the NERVE ENDING of the motor unit?

Botulism

Lambert Eaton Disease

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what are the disorders associated with lesions in the SYNAPTIC CLEFT

Acetycholine esterase absent

Myasthenia

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what are the disorders associated with lesions in the END PLATE

Myasthenia graves

nACh-receptor

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what are the disorders associated with lesions in the muscle fiber

Myotonias

muscular dystrophy

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Polio virus can affect the whole body but most cases what is affected?

motor neurons in the ventral horn

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how is polio transmitted?

person to person (nose, mouth, and fecal)

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how would one prevent themselves from getting the polio virus?

VACCINATE!!! (90% effective)

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What are the symptoms of severe cases of polio?

Permanent paralysis or death :(

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what bacteria is associated with botulism?

Clostridium botulinum (anerobic bacteria)

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what is the mechanism of botulism?

Stops ACh vesicles from docking at the NMJ by acting on the presynaptic proteins

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why does botulism result in paralysis??

the inhibition of ACh exocytosis, results in the paralysis

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what are three ways to be infected with botulism toxin?

Eating food that contains botulism toxin
Infection fo a wound with Clostridium botulinum
Consuming spores of Clostridium Botulinum

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What is the mechanism of action of the black widow spider toxin (alpha latrotoxin)

the toxin causes a massive release of ACh

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why does a person develop tetanus and pain contraction of the muscle with the alpha latrotoxin?

The venom travels via the lymphatic system to the blood eventually reaching the nerve endings to cause the massive release of ACh and then tetanus and painful contraction of the muscles.

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what is the CLASSIC characteristic of alpha latrotoxin?

cramping

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what is the mechanism of action of the beta-bungarotoxin?

toxin in snake venom.

reduces ACh release by actin on proteins in the nerve terminals involved in exocytosis.

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What is the mechanism of action for Curare or delta-tubocurarine?

known as the arrowhead poison

found in plants and is a reversible nAChR antagonist. (aka blocks the ach receptors)

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describe the mechanism of action for Lambert eaton syndrome

Autoimmune disease where circulating antibodies are directed against voltage gated Ca2+ channels in the motor neuron terminals. so therefore causes an insufficient release of ACh.

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what will happen to someone with lambert eaton syndrome after continued attempts at muscular contraction?

allows the synaptic concentration of ACh to rise sufficiently until it reaches a concentration sufficient to elicit a proper contraction.

what carcinoma is lambert eaton usually associated with??

Oat cell carcinoma of the lung

what are the three physiological changes at the end plate of lambert eaton syndrome

1. Reduced amplitude of EPP 2. Many EPPs do not attain threshold in muscle fibers 3. Amplitude of MiniEPP is unchanged

what is the classic sign you would see on examination with a patient who has lambert eaton syndrome

strength increases with activity. | reflexes are decreased

what is evident in the EMG of a patient with lambert eaton syndrome?

WAXING is evident after repeated nerve stimulation

what are some treatments for lambert eaton syndrome?

1. Remove underlying tumor and give immunosuppressive drugs. 2. Plasma exchange 3. Calcium gluconate to enhance Ca2+ influx 4. 4-aminopyridine will block K channels that increases presynaptic impulse duration causing increase Ca2+ release and eventually improve ACh release.

The first form of myasthenia (muscle weakness) is AChE deficiency. Explain the mechanism

1. Causes increased and prolonged EPP | 2. Temporal summation will easily cause desensitization (depolarizing blockade)

The second form of myasthenia (muscle weakness) is slow channel syndrome. Explain the mechanism

1. Binding of ACh to nAChR causes prolonged opening of the ACh receptor channel 2. Channels open for too long causes prolonged depolarization resulting in a depolarizing blockade

what are symptoms of slow channel syndrome?

muscle weakness, rapid fatigue and progressive atrophy

what is the third form of congenital myasthenia (muscle weakness)

abnormal binding of ACh with nAChR

what is the fourth form of congenital myasthenia?

ACh gated channels have extremely brief open times!

what age does myasthenia (muscle weakness) usually appear in patients?

before the age of two

The main manifestation of myasthenia gravis is weakness of voluntary muscles, when does the weakness improve and when does it weaken?

improves after rest and worsens with muscular activity. this is seen on the EMG as a waning pattern

what mechanism causes weakness in myasthenia gravis?

Autoimmune antibodies against nAChR which blocks ACh's ability to bind to its receptor.

what structural changes are seen in the end plate of myasthenia gravis? (due to cross linking)

1. Fewer nAChR 2. Wider cleft 3. Smaller/shadow junctional folds

what are the general symptoms of a patient with myasthenia gravis?

1. weakness of voluntary muscles (improves with rest) 2. Difficulty swallowing 3. Late day paralysis 4. Myasthenic Crisis (difficulty breathing) 5. Diplopia (first symptom)

In myasthenia gravis, do antibodies compete with ACh for the binding sites on subunits??

no antibodies do not compete | they actually crosslink with neighboring nAcHRs

Myasthenia gravis is associated sometimes with what types of tumors?

thymus gland tumors

what is the classic pattern seen on EMG of someone with myasthenia gravis?

in repetitive stimulation waning pattern. | initially patients are okay but with stimulation patients become weaker and weaker

what are some treatments of myasthenia gravis?

1. Neostigmine or Pyridostigmine (AChE inhibitors) 2. Prednisone (after other drugs have failed) 3. Surgical removal of the thymus

Myotonia Congenita is a genetic disease of what?

fewer chloride channels are expressed and inserted into the cell membrane.

In normal muscle, what do chloride channels do?

numerous chloride channels help to keep the membrane potential close to Ecl during recovery from an action potential when potassium ions are accumulating in the transverse tubular system.

without the proper amount of chloride channels in myotonia congenita, what will the patient present with?

``` increase excitability (due to smaller depolarizations required to evoke an action potential) and decreased relaxation ```

What is the main symptom seen in myotonia congenita?

slower muscle relaxation | so patients have muscle stiffness and hypertrophy

what muscle protein is absent in Duchenne Muscular Dystrophy?

Dystrophin

what do most patients die from in Duchenne Muscular Dystrophy?

Cardiovascular or respiratory insufficiency

what is Lower Motor Neuron Syndrome?

2nd order neurons which stimulate the muscle are lost

where is the lesion at in LMN syndrome?

on the motor axon or | at the soma in the spinal cord or brainstem

what are the causes of LMN syndrome?

Viral Infection (polio) Trauma Neuro degenerative

what are the signs/symptoms associated with LMN syndrome?

``` weakness/paralysis loss of reflexes flaccid paralysis fasciculations (irregular spontaneous contractions) fibrillations (spontaneous contractions) muscular atrophy ```

what two symptoms of LMN syndrome correlate with denervation of muscle fibers?

Fasciculations (cause visible and palpable twitches on the surface of the body) Fibrillations (spontaneous electrical events visible on an EMG)

in a normal muscle fiber, normal nerve stimulation leads to what?

aggregation of nAChRs under nerve endings

what happens to nAChRs if muscle is denervated?

Following denervation of nAChRs, they become distributed across the entire surface of the muscle cell