Skeletal muscle contraction disorders

Question 1

What is compartment syndrome?

Answer 1

Internal bleeding or swelling within a muscle compartment… increases the pressure in the compartment… restricting blood flow and damaging BVs and nerves.

Can be acute (after trauma) - is a medical emergency- or chronic (during exercise).

Question 2

What are the symptoms of acute compartment syndrome?

Answer 2

• deep, constant, poorly localised pain
• pain aggravated by passive stretch of muscle group
• parathesia (= altered sensation, eg pins and needles)
• compartment may feel tense and firm
• swollen, shiny skin, sometimes with obvious bruising
• prolonged capillary refill time

Question 3

How is acute compartment syndrome usually treated?

Answer 3

Fasciotomy (incision to open skin and fascia to relieve pressure), subsequently covered by skin graft

Question 4

What is fasciculation?

Answer 4

Small, local, involuntary muscle contractions and relaxation. May be visible under skin.

Question 5

What is large-fibre sensory neuropathy?

Answer 5

Patients are able to perform accurate movements whilst watching the affected limb, but in the absence of vision, small movements are grossly inaccurate.

Question 6

What is hypotonia? When is it most common?

Answer 6

• Lack of skeletal muscle tone

- In babies soon after birth (floppy baby syndrome)

Question 7

Give examples of pathological conditions in which hypotonia is a symptom.

Answer 7

1. Damage to the motor cortex, cerebellum or spinal cord
   - cerebral or spinal neural shock
   - lesions of the cerebellum
   - lesions of sensory afferents from muscle spindles, e.g. charcot-marie-tooth disease
   - lesions of lower motor neurons, e.g. polyneuritis, spinal muscular atrophy (loss of motor neurons)
2. Primary degeneration of the muscle itself (myopathies)
   - muscular dystrophies

Question 8

What is malignant hyperthermia and how is this condition triggered?

Answer 8

• Rare life-threatening polymorphism in ryanodine receptor (most common genetic cause) causes it to be activated by some volatile anaesthetic agents and succinylcholine (neuromuscular blocking agent).
• Drug-induced receptor activation leads to massive increase in intracellular calcium from intracellular stores… SERCA pump (requires ATP) working at dramaticlally increased rate… excessive heat production.

Question 9

How can malignant hyperthermia patients be treated?

Answer 9

Dantrolene = muscle relaxant which antagonises RyR.

Question 10

What is myotonia?

Answer 10

inability to relax muscles at will

Question 11

Which types of voltage-gated channelopathies can cause myotonia?

Answer 11

1. Cl- channel (CLCN1) - myotonia congenita

2. Na+ channel (alpha subunit) - potassium aggravated myotonia, paramytonia congenita, hyperkalemic periodic paralysis

Question 12

Which types of voltage-gated channelopathies can cause period paralyses?

Answer 12

1. Na+ channel (alpha subunit) - paramyotonia congenita, hyperkalaemic periodic paralysis
2. Ca2+ channel (alpha1s subunit) - hypokalaemic periodic paralysis

Question 13

What is the genetic cause of myotonia congenita and what are its symptoms?

Answer 13

Mutation in chloride channel CLCN1. Can be recessive (Becker type) or dominant (Thomsen type) depending on mutation type.

Symptoms:

• muscle stiffness (esp in leg muscles, may be enhanced by cold and inactivity, often relieved by exercise)
• muscle hypertrophy

Question 14

Explain why mutation if CLCN1 Cl- channel in myotonia congenita affects muscle APs.

Answer 14

• In skeletal muscle, about 70% of conductance in resting fibres is due to Cl- flow (in most excitable cells, Na+ and K+ permeabilities are the major determinants).
• Cl- ions do not actively set the resting potential but when MP deviates from rest levels, large Cl- currents flow to return the membrane voltage to prior resting value.
• In myotonia congenita, this buffering capacity from Cl- is lost and myotonic discharge results.