NMJ d/o

Question 1

What are the skeletal fibres innervated by?

Answer 1

by motor neurones, whose cell bodies reside in the VENTRAL horn of the spinal cord

Question 2

What is a motor end plate?

Answer 2

it is the synapse between the motor neurones and muscle

Question 3

What occurs when the AP reaches the axon terminale?

Answer 3

• 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

Question 4

WHat occurs with the release of ACh into the synaptic cleft?

Answer 4

Acetylcholine binds to the Ach-receptor

• opening up Na+/K+ channels
• depolarization starts an AP at the motor end plate

Question 5

What is the role of Acetylcholinesterase?

Answer 5

• breaks down ACh into acetyl and choline

- choline will then be sequestered into vesicles in the pre-synaptic neurone

Question 6

What is Curare?

Answer 6

• 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

Question 7

Name a pre-synaptic disorder.

Answer 7

Botulism

• by Clostridium Botulinum (present in the SOIL)
• seen in IV drug users (black tar heroin)

Question 8

How does Cl.Botulinum bring about its action?

Answer 8

• 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

Question 9

How does Botulism present as?

Answer 9

-rapid weakness over 6 hrs (NO SENSORY loss)

Question 10

What occurs in Lambert Eaton Myasthenic Syndrome (LEMS)?

Answer 10

• Anti-bodies to presynaptic calcium channels leads to LESS vesicle release.

Question 11

What is LEMS a/w?

Answer 11

• underlying small cell lung carcinoma

Question 12

How to rx LEMS?

Answer 12

3-4 diaminopyridine

Amifampridine

Question 13

What is the most common D/O of the neuromusclular jxn? What brings about this condition?

Answer 13

-Myasthenia Gravis - an autoimmune condition with Antibodies to AChR
>reduces no. of FUNCTIONING receptors leading to FATIGUABILITY and WEAKNESS

Question 14

What are the signs of M.G?

Answer 14

• ptosis
• rapid onset of respiratory d.o
• lower back weakness
• appears sad (B/L facial weakness)

Question 15

When may the symptoms of Myasthenia Gravis begin to show?

Answer 15

• when ACh receptors reduce to 30% of normal

- –reduced AChR may FLATTEN endplate folds

Question 16

State the issues brought out by the ACh-Abs? (3)

Answer 16

1. blocks Ach from binding to its receptors
2. reduces the no. of FUNCTIONING Ach-R
3. inflammatory cascade is brought on to the folds of the end plates; flattening it out

Question 17

What specific gland is said to play a role in MG?

Answer 17

• the thymus

- 75% have thyoma or Hyperplasia

Question 18

When is the usual onset of Myasthenia Gravis in Males and Females?

Answer 18

• M: 60s or 70s
• F: 30s

F:M= 3:2

Question 19

What is the pattern of weakness like in pts with MG?

Answer 19

• FLUCTUATING

- worse at the END of the day

Question 20

What is most common presentation of MG?

Answer 20

• EXTRAocular weakness, facial and bulbar weakness

- PROXIMAL limb weakness

Question 21

Why do MG pts lose weight?

Answer 21

• as they get tired of chewing

- thus won’t be eating as much

Question 22

What is Myasthenic Crisis?

Answer 22

• complication of MG
• worsening of the condition results in respiratory failure
• requiring mechanical intubation and ventilation

Question 23

What acute treatment is given for MG?

Answer 23

• acetylcholine-esterase INHIBITOR (pyridostigmine)
• IV Immunoglobulin
• THYMECTOMY (even w.o abnormality)

Question 24

If symptomatic rx does

not work for MG…?

Answer 24

• steroids (PREDNISOLONE or steroid sparing agents –AZATHIOPRINE/MYCOPLENOLATE
• plasma exchange/immunoglobulin

Question 25

Why is prednisolone used for MG?

Answer 25

-leads to remission and marked improvement in 70% of patients with OCULAR and generalized weakness

Question 26

Why is azathioprine used for MG?

Answer 26

- It's an immunosuppressant, dampening the prodn of Abs by the immune system

Question 27

Primary causes of death by MG? (2)

Answer 27

- respiratory failure (in the elderly) | - aspiration pneumonia

Question 28

What are the different types of muscle fibres? (3)

Answer 28

TYPE I- slow oxidative TYPE IIa- fast oxidative (aerobic metabolism) TYPE IIb- fast glycolytic

Question 29

Which muscle fibre type is easily fatigued?

Answer 29

type IIb

Question 30

What are fasciculations and what precipitates it?

Answer 30

- visible, fast and spontaneous TWITCH | - seen in healthy muscleswith stress, caffeine, fatigue

Question 31

Why do fasciculations occurs?

Answer 31

- when a denervated muscle becomes hyperexcitable | - occurs as a sign of motor neurone disease, not MUSCLE.

Question 32

Define myotonia.

Answer 32

- the delayed relaxation/sustained contraction of the muscle - hard to stop one shaking their hands

Question 33

State 4 signs of muscle disease.

Answer 33

1. muscle wasting 2. hyporeflexia, 3. muscle WEAKENING 3. myalgia

Question 34

When may myotonia occur?

Answer 34

- usually hereditary | - involves chloride channels

Question 35

Name 2 immun-mediated musclular d/os?

Answer 35

POLYMYOSITIS | DERMATOMYOSITIS

Question 36

How does polymyositis present as? (3)

Answer 36

- symmetrical - progressive, PROXIMAL weakness - develops over weeks to months

Question 37

What is serum finding of Polymyositis?

Answer 37

- raised CK | - responds to Steroid

Question 38

How is Dermatomyositis different?

Answer 38

- clinically similar but a/w skin lesions - "heliotrope rash" on face (red rash on swollen eyelids) - ---50% have underlying MALIGNANCY

Question 39

What is Inclusion Body Myositis?

Answer 39

- degenerative muscle condition - progressive weakness in 6th decade of life - thumb is spared - relentless Muscle wasting

Question 40

What is the commonest muscular dystrophy? What genetic anomaly results in this?

Answer 40

- MYOTONIC DYSTROPHY - ---autosomal dominant ; trinucleotide repeat d.o - ---> multisystem involvement

Question 41

How does myotonic dystrophy present as?

Answer 41

- myotonia, weakness, ptosis, frontal balding, cardiac defects

Question 42

What are muscular dystrophies? (3)

Answer 42

- INHERITED - NON-inflammatory (unlike myositis) - no central or peripheral nerve problem

Question 43

Name 2 muscular dystrophies.

Answer 43

- Duchenne | - BECKER Muscular dystrophy

Question 44

Name 3 infective causes of muscular d.o..

Answer 44

- coxsacchie - Trypanosomiasis Cistercercosis (pork) - borrelia

Question 45

What is rhabdomyolysis?

Answer 45

- 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

Question 46

What is the triad of rhabdomyolysis?

Answer 46

- myalgia, muscle weakness, myoglobinuria | - Acute renal failure (reduced urine and dark red urine) and DIC

Question 47

What are the first few signs of Myasthenia Gravis?

Answer 47

- ocular conditions | diplopia and ptosis

Question 48

Name causes of NMJ disruption.

Answer 48

1. Mysathenia Gravis- Abs to the Ach-R in POST-synaptic cleft 2. LAMBERT-EATON $- Abs to the voltage-gated calcium channels 3. ORGANOPHOSPHATE poisoning- inhibition to ACh-E

Question 49

Drugs that may cause symmetrical, often proximal muscular weakness.

Answer 49

- illicit drugs (COCAINE, Heroine) - alcohol - corticosteroids - others: HMG-CoA Reductase, ziduvodine, colchicine, penicillinamine, anti-malarial drugs, contraceptives, diuretics

Question 50

What are some medical (and cosmetic) uses of botulinum toxin? -

Answer 50

- muscle dystonia - dysphonia - SWEATING - muscle TWITCHING around the eyes

Question 51

What autoimmune conditions is Myasthenia Gravis a.w?

Answer 51

- DM - thyroid d.o - pernicious anemia - rheumatoid - SLE