Disorders Of Muscle

Question 0

Outline the physiology of the neuromuscular junction and describe the pathogenesis and clinical features of myasthenia gravis

Answer 0

Autoimmune destruction of end-plate ACh receptors, loss of junctional folds at end-plate, widening of synaptic cleft
Symptoms - fatigue, sudden falling (reduced ACh release), drooping eyelids, double vision
Treatment - acetylcholinesterase inhibitors (neostigmine, physostigmine)

Question 1

Describe the process of skeletal muscle remodelling and it’s relevance to atrophy and hypertrophy

Answer 1

Remodelling of skeletal muscle is a continuous process
Atrophy (destruction > replacement):
Disuse - muscle fibres shrink and weaken –> loss of protein –> reduced fibre diameter –> loss of power
Age - muscle mass decreases >30
Denervation - muscle no longer receives contractile signals –> weakness, flaccidity, fasciculations (twitching) –> degeneration of muscle fibres –> replaced with fibrous and fatty tissue
Hypertrophy (replacement > destruction):
Increase in muscle mass –> more contractile proteins –> increase in fibre diameter

Question 2

Starve how neuromuscular transmission is disrupted in botulism and organophosphate poisoning

Answer 2

Botulism (Botox) - blocks ACh receptors

Organophosphate poisoning - irreversibly inhibits ACh (muscle stays contracted)

Question 3

Describe the pathophysiology of Duchenne Muscular Dystrophy (DMD)

Answer 3

Genetic - complete absence of dystrophin
Muscle fibres tear themselves apart on contraction, creatine kinase released into serum, calcium enters cell causing cell death (necrosis), pseudohypertrophy (swelling) –> fat and connective tissue replace muscle fibres
Signs/symptoms - early onset, Gower’s sign, contractures
Treatment - steroid therapy, gene therapy

Question 4

Outline the pathophysiology of malignant hyperthermia

Answer 4

Autosomal dominant
Life threatening reaction caused by some drugs used in general anaesthesia - volatile anaesthetic agents, succinylcholine (neuromuscular blocking agent, non-competitively inhibits ACh, slowly degraded by butyrylcholinesterase)
Uncontrolled increase in skeletal muscle oxidative metabolism –> generates heat –> circulatory collapse –> death
Treatment - discontinuation of triggering agents, administration of dantrolene (muscle relaxant prevents release of calcium)