Diseases Of NMJ Flashcards

Question

What are the physiological changes at end plate in lambert eaton syndrome?

Answer 1

Physiological Changes at End Plate – Amplitude of Mini EPP is unchanged – Reduced amplitude of EPP • Reduced quantal content – Many EPPs do not attain threshold in muscle fibers – Waxing response in EMG(relates to facilitating neuromuscular block)

Answer 2

Therapy for Lambert-Eaton Syndrome – Removal of underlying tumor and immunosuppressive drugs – Plasma exchange – Calcium gluconate to enhance calcium influx into nerve terminal – 4-aminopyridine (potassium channel blocker) to prolong presynaptic action potential and improve transmitter release

Answer 3

* Many forms of congenital Myasthenia | * They usually present at birth and show signs and symptoms before the age of two years

Answer 4

* Many forms of congenital Myasthenia | * They usually present at birth and show signs and symptoms before the age of two years

Answer 5

1. Deficiency of ACh-esterase in synaptic cleft at end plate – EPP amplitude is larger and more prolonged than normal – Motor nerve stimuli separated by long intervals cause single muscle twitches (indicating increased temporal summation) – Motor nerve stimuli delivered in trains produce temporal summation of EPPs and cause depolarization block of muscle ``` 2. Prolonged opening of channels • 'Slow Channel Syndrome' – Inherited rare condition presents at birth or early childhood • Muscle weakness • Rapid fatigue – Prolonged opening of the ACh channel – A resultant depolarization block ``` Other forms – One form where the binding of ACh to nAChR is abnormal – One form where the ACh-gated channels have very brief opening times

Answer 6

– Chronic autoimmune disease • Antibodies to nAChRs develop and reduce transmission at the NMJ – Genetic susceptibility

Answer 7

Symptoms – Weakness of somatic muscles • Not associated with denervation – Fatigability – Temporary restoration of strength after rest

Answer 8

Interaction of Antibody and nAChR – Antibodies bind to Alpha subunits of nAChR – Antibodies do not compete with ACh for binding sites on subunits – Antibodies cross-link neighboring nAChRs

Answer 9

Dynamics of cross-linked nAChRs in end plate membrane – Endocytosis of nAChRs in end plate membranes – Lysosomal destruction – Enhanced removal rate of nAChRs but no enhanced rate of insertion of nAChRs into end plate membrane – Fall of density of nAChRs at end plate

Answer 10

Structional Changes at the End Plate – Fewer nAChRs – Wider synaptic cleft – Smaller junctional folds

Answer 11

Clinical features: – incidence 1:10,000 – xx : xy = 2:1 (all races), xx age 20-30 , xy age 60-70 – Typical onset: 1st symptom is diplopia in the afternoon, disappears following morning – Gradual increase in duration of diplopia, followed by ptosis – Restriction of extraocular movements – Ptosis compensated by backward tilting of the head and wrinkling of frontalis muscle

Answer 12

Diagnosis: – Repeated clenching and unclenching of fist → rapid loss of strength – Tensilon test (edrophonium): after injection of Tensilon (ACh- esterase inhibitor) muscular strength recovers temporarily – Ice pack – Anti- AChR antibody testing – EMG

Answer 13

``` Therapies: – Thymectomy – Immunosuppressing medication: azathioprine, corticosteroids – Pyridostigmine (AChE inhibitor) ``` • Myasthenic crisis: medical emergency – Causes: sudden onset of disease, patient becomes refractory to drug – ICU treatment, intubation and respirator therapy

Answer 14

* Myotonia: delayed relaxation of muscle after voluntary contraction or percussion. * Myotonia congenita is due to a mutation in the ClCN1 chloride channel. * The chloride channel defect causes increased excitability * Muscular hypertrophy can develop despite little physical activity in these patients.

Answer 15

Smaller depolarization is required to evoke an action potential and may even cause a train of action potentials Repetitive firing of the muscle fiber after motor nerve stimulation ceases Delayed relaxation phase of the neuronal evoked muscular contraction

Answer 16

MuscularDystrophy Group of disorders that characteristics of progressive muscular weakness Duchenne Muscular Dystrophy Most common X-linked recessive disorder of muscles Onset in early childhood Muscle weakness develops progressively Patients die from cardiovascular and respiratory insufficiency Cause: absence of muscle protein - Dystrophin

Answer 17

• Onset: 3–5 years of age • Proximal muscle weakness and calf hypertrophy is common * difficulty in running or getting up from the ground, frequent falls, or toe-walking * High serum marker levels of CK

Answer 18

Lower Motor Neurons (LMNS) - primary motor neurons of the spinal cord and brain stem that directly innervate skeletal muscles. • Upper Motor Neurons -neurons that originate in higher regions of the brain (cortex...) and synapse on lower motor neurons.

Answer 19

``` Signs of LMNS – Muscle weakness (paresis) – Flaccid paralysis – Loss of tendon reflexes – Fasciculations – Fibrillations – Developing muscle atrophy → death of muscle ```

Answer 20

Fasciculations and fibrillations are signs that muscle fibers are undergoing de-nervation. • Fasciculations: – Fasciculationsareirregularspontaneouscontractionsofthemuscle fibers in motor units giving visible twitches at surface of body. Fasciculations by themselves are not always a sign of motor neuron damage https://www.youtube.com/watch?v=u421daHAgpY • Fibrillations (EMG!) – arespontaneouscontractionsofsinglemusclefibers.

Answer 21

In embryonic muscle fiber the nAChRs are distributed across the entire surface In adult muscle fiber the pattern of nerve stimulation leads to aggregation of nAChRs under nerve endin