MM4

Question 1

TorF

Perimysium surrounds muscle fibres.

Answer 1

F- perimysium surrounds muscle fascicle. Endomysium surrounds muscle fibres.
(4.1)

Question 2

Describe the process of excitation-contraction coupling in skeletal muscle

Answer 2

1. action potential reaches terminal of motor neuron and triggers release of Ach from axon terminal.
2. Ach binds to receptor on muscle, triggers opening of Na+ channels. Na+ influx causes depolarisation of membrane. Travels down t-tubule.
3. Depolarisation of t-tubule activates DHP receptor which is mechanically linked to Ryanodine Receptor on SR
4. RyR opens, allowing Ca to leak out of SR and enter cytosol.
5. Ca binds to troponin causing tropomyosin to move and reveal myosin binding site on actin filament

(4.1)

Question 3

TorF, it is the bidning of ATP to the myosin head that causes cross-bridge formation

Answer 3

F- ATP binding to myosin head primes and cocks head to be in correct position to form crossbridge. But actual cross bridge is formed when ATP is hydrolysed.

(4.1)

Question 4

TorF
According to the sliding filament model, as sarcomere length shortens in muscle contraction, the A bands are shortened and the Z lines move closer together

Answer 4

F- A bands stay the same length, it’s the I bands that shorten. Z lines move closer together

(4.1)

Question 5

What are the two major points of ATP utilisation in muscle contraction?

Answer 5

1. hydrolysis of ATP so myosin head can form cross bridge in excitation-contraction coupling.
2. reuptake of calcium into SR

(4.1)

Question 6

What three factors influence whole-muscle tension?

Answer 6

1. Tension developed by each individual muscle fiber (depends on frequency of stimulation and length of fibre at onset of contraction)
2. Number of muscle fibres contracting within a muscle
3. Cross-sectional area of muscle

(4.2)

Question 7

TorF

Muscles that produce precise, delicate movements contain a greater fibre to motor unit ratio

Answer 7

F- precise delicate movements require precise control, therefore less fibres innervate by a single motor neuron

(4.2)

Question 8

TorF

Increase in cross sectional area is primarily due to hypertrophy

Answer 8

T- increase in cell size rather than number

4.2

Question 9

What is the difference between isotonic and isometric contraction?

Answer 9

Isometric contraction- muscle has not shortened. Sarcomeres shorten, generating force, bu elastic elements stretch, allowing muscle length to remain the same.
Isotonic contraction- sarcomeres shorten more but, because elastic elements are already stretched, the entire muscle must shorten.

(4.2)

Question 10

Which of the following do not contribute to a muscle’s speed of contraction:

a. excitation-contraction coupling
b. cross-bridge cycling rate
c. fibre diameter or cross-sectional area
d. SR ca2+ reuptake

Answer 10

c. – fibre diameter or CSA don’t contribute to speed of contraction, but contribute to maximal force production of muscle.
(4. 2)

Question 11

TorF

Type IIx muscle fibres have high mitochondria and myoglobin content

Answer 11

F- type IIx fibres are fast twich glycolytic fibres that have low oxidative capacity. Therefore it has low mitochondria and myoglobin content and is considered “white” muscle.

(4.2)

Question 12

Which muscle fibre type has the largest fibre diameter?
Which type is most fatigue resistant?
Which muscle fibre type are endurance athletes likely to have more of?
Which muscle fibre type do we lose with ageing?

Answer 12

1. Type IIx
2. Type I
3. Type I (60-80%)
4. Type II (+ reduced number of satellite cells)

(4.2)

Question 13

Which area of the brain coordinates stereotyped motor patterns related to actions like eating, drinking and sexual activity?

Answer 13

Hypothalamus.

4.3, slide 8

Question 14

Which higher order brain centre plays a large role in fine motor control?

Answer 14

Cerebellum

4.3, slide 22

Question 15

Of the principal descending motor pathways- corticospinal, medial and lateral pathways- which is involved in conscious motor control of skeletal muscle (as opposed to subconscious regulation and reflex control)?

Answer 15

Corticospinal pathway

4.3, slide 10

Question 16

TorF

Muscle spindles and golgi tendon organ both detect the length of a muscle and its velocity of contraction

Answer 16

F- only muscle spindles detect the length of a muscle and its velocity of contraction. Gogli tendon organs detect the force of contraction

(4.3)

Question 17

TorF

Interneurons only project ipsilaterally up and down the spinal cord and mediate both inhibitory and excitatory actions

Answer 17

F- interneurons project both ipsilaterally and contralaterally. They can mediate both inhibitory and excitatory actions.

(4.3)

Question 18

Which of the following are false when there is a lesion to upper motor neuron (above the anterior horn cell or motor nuclei):

a. paralysis on ipsilateral side to lesion
b. muscle weakness, lack of muscle control
c. slow muscle movements
d. no muscle atrophy

Answer 18

a is incorrect; paralysis is on the contralateral side to lesion because upper motor neurons crossover. Muscle weakness, slow movements and lack of muscle control are all involved and there is no muscle atrophy.

(4.3, slide 23)

Question 19

Which of the following is true when there is a lesion to lower motor neuron:

a. Lower motor neuron lesions is a lesion to the neuron that travels from anterior horn to muscles
b. results in contralateral hypoactive reflexes
c. there is generalised muscle paralysis to the whole region
d. there is no muscle atrophy

Answer 19

a is true.
b- results in ipsilateral hypoactive reflexes because motor neurons don’t crossover after the level of spinal cord
c- there is paralysis of specific muscles because the injury is to a specific motor neuron not their input.
d- there is flaccid muscle and atrophy

(4.3, slide 24)

Question 20

Lesions of the cerebellum cause what kind dysfunction?

Answer 20

• General loss of coordination
• Loss of balance
• Inaccurate range and direction of movement
• Inability to move rapidly and stop quickly

(4.3)

Question 21

which of the following about Duchenne Muscular Dystrophy is false:

a. Most common type of muscular dystrophy (incidence ~1:3500 live male births)
b. X-linked recessive disorder primarily afflicting males
c. Gower’s sign and waddling gate are characteristics signs during the early non-ambulatory stage of DMD
d. Dystrophin links the actin cytoskeleton directly to the collage in basal lamina to stabilise muscle architecture

Answer 21

d is incorrect- dystrophin links the actin cytoskeleton with basal lamina via the Dystrophin associated complex and laminin

(4.4)

Question 22

What is the most severe type of myotonic disorders? (Myotonic dystrophy, Congenital myotonia, Potassium aggravate myotonia)

Answer 22

Myotonic dystrophy

4.4

Question 23

TorF

1. Muscular dystrophy 1 (DM1) is due to mutation in the DM protein kinase gene
2. DM2 is due to mutation in zinc finger protein 9 gene
3. Number of repeats correlates with age of onset and severity of the disease
4. DM2 is more severe than DM1
5. inheritance is autosomal dominant

Answer 23

1. T
2. T
3. T
4. F
5. T

(4.4)

Question 24

Which of the following is not an additional pathology of myotonic dystrophy (in addition to myotonia and muscle weakness)?

a. Cardiomyopathy and conduction defects
b. Nutrient malabsorption
c. Cataracts
d. Hypogonadism
e. Mild cognitive impairment

Answer 24

B is incorrect. The others are all involved

4.4

Question 25

congenital Myotonia is associated with mutation in which gene?

Answer 25

CLCN1 gene, 80 mutations in this gene have been identified so far (4.4)

Question 26

TorF 1. Becker’s and Thomsen’s disease are both recessive inheritance 2. Thomsen’s is more severe than becker’s disease 3. Age of onset of both Becker’s and Thomsen’s disease is adulthood (>40years)

Answer 26

1. F- becker’s is recessive and thomsen’s is dominant inheritance 2. F- the individual mutation determines the severity of the disease 3. F- age of onset of Becker’s is late adulthood (>40years) while Thomsen’s is infant onset. (4.4)

Question 27

TorF 1. Mitochodrial myopathies are associated with other pathologies such as cognitive impairment, cardiomyopathies and lactic acidosis 2. Inheritance is maternal

Answer 27

1. T 2. T (4.4)

Question 28

Which of the inherited muscle disorders are “ragged red fibres” and increased sub-sarcolemmal SDH staining found in muscle biopsies?

Answer 28

Mitochondrial myopathies | 4.4, slide 23

Question 29

Which of the following about the definition of Sarcopenia is false a. Involves loss of muscle mass b. decrease in myofibre length c. loss of individual myofibes d. infiltration of fat and connective tissue

Answer 29

b is false- there is decrease in myofibre cross sectional area (4.5)

Question 30

TorF | Regular muscle strengthening activities can stop sarcopenia.

Answer 30

F- regular activity only slows, not halts, sarcopenia | (4.5, slide 7)

Question 31

Which of the following is false about Muscle atrophy in COPD: a. there is loss of muscle strength and fatigue resistance b. decreased fibre cross-sectional area c. decrease in type 2 fibres

Answer 31

c. is false- there is decrease in type 1 fibres, the fatigue resistant fibres. (4. 5)

Question 32

Muscle wasting in chronic disease involves systemic inflammation that causes excessive protein degradation. Explain a major source of inflammation in - Sarcopenia - Cancer cachexia - COPD

Answer 32

- In sarcopenia there is decreased mitochondrial function which increases reactive oxygen species production and activates inflammatory cascades. - Cancer cachexia: factors released by the tumour itself or increased circulating inflammatory cytokines as a consequence of the tumour. - COPD: systemic inflammation results from local respiratory inflammation (4. 5)

Question 33

Sytsemic inflammation acts on which major regulator of metabolic pathways to cause excessive protein degradation?

Answer 33

Inflammation inhibits action of AKT resulting in - Increased Ub-proteasome mediated protein degradation - Decreased protein synthesis (4.5)

Question 34

TorF In type 2 diabetes, reduced glucose uptake into muscle accounts for most of the reduction in glucose disposal in diabetic patients

Answer 34

T | 4.5, slide 20

Question 35

TorF | Reduced AS160 activation by insulin appears to be responsible for insulin resistance in Type 2 diabetes

Answer 35

T- Insulin should activate AKT to activate AS160 which is responsible for vesicle targeting of GLUT4 transporters to the membrane. When this activation by insulin becomes ineffective, there is decreased membrane expression of GLUT4 transporters on muscle, so the muscle can’t take up glucose. (4.5, slide 21)

Question 36

TorF | Oxidative stress is a major cause of insulin resistance in skeletal muscle

Answer 36

T | 4.5, slide 22

Question 37

What enzyme do Statins act on to reduce cholesterol synthesis?

Answer 37

HMGCoA reductase. Catalyses the conversion of HMGCoA into mevalonate. (4.5)

Question 38

What is the most severe adverse effect of statins?

Answer 38

Rhabdomyolysis- which may result in acute renal failure, DIC and death

Question 39

Give a basic description of the proposed mechanism of statin-induced myopathy:

Answer 39

Statins inhibit the enzyme required for conversion from HMGCoA to Mevalonate. Mevalonate is not only a precursor for cholesterol but also of a number of intermediary metabolites. - Membrane channel theory: It is thought that it plays important roles in posttranscriptional lipid modification of proteins that are required for the integrity of muscle membrane channels which leads to muscle membrane hyperexcitability similar to that observed in muscle myotonia. - Mitochondrial theory- based on the fact that statins inhibit the synthesis of mevalonate a precursor for important factors in the ETC. - Impairment of calcium homeostasis leading to symptoms of myalgia or cramps - Induction of apoptosis