What are the 4 main functions of skeletal muscle?
1) Stability of joints
2) Movement
3) Posture
4) Heat generation
How often are the actin and myosin filaments within skeletal muscle replaced?
Every 2 weeks, on average
How can the number of fibers within a muscle be changed?
Cannot increase or decrease number of fibres present.
How can you change the size of a muscle, as the number of fibres present cannot change?
Number of proteins present in the fiber (actin and myosin) can increase or decrease, changing the size of the muscle
What is the name given to muscle wasting?
Muscle atrophy
What is the name given to describe an increase in muscle size?
Muscle hypertrophy
How does regular exercise affect the ATPase activity in skeletal muscle?
It increases the amount of ATPase activity present on the myosin II molecules
How does regular exercise affect the t tubules present in skeletal muscle?
It increases the density of t tubules systems throughout the muscle
How does regular exercise affect the number of contractile proteins present in skeletal muscle?
It increases the number of contractile proteins (actin and myosin) present within muscle fibers
Why does an increase in protein in skeletal muscle lead to increase in muscle strength?
Strength is determined by the amount of cross-bridges that can occur between the actin and myosin in a muscle fiber. If increased protein, then increased actin and myosin = increased number of cross-bridges.
Why does high resistance exercise cause muscle growth?
It stimulates protein synthesis to increase the strength of the muscle. More actin/myosin = fatter muscle fibres = larger muscle
Why does endurance exercise have more health benefits compared to high resistance training?
Over time it causes the muscle to shift to an oxidative metabolism, which causes the muscles to use lipids rather than glucose from the blood, so reduces amount of lipid in blood.
How does bed rest and limb immobilisation affect skeletal muscle?
It causes disuse atrophy, which results in loss of protein and power of muscles.
Define sarcopenia:
The loss of skeletal muscle mass and strength, as a result of ageing.
After what age does muscle atrophy begin as a natural process?
After 30 years old.
Why does sarcopenia affect temperature regulation?
Not enough muscle mass to generate enough heat via shivering.
What type of motor neurones innervate skeletal muscle?
Lower motor neurones
What are the 2 main signs of a lower motor neuron lesion?
1) Muscle weakness
2) Muscle atrophy
Define lower motor neuron lesion:
Lesion affecting any motor neuron which runs from the anterior horn to a skeletal muscle
Re innervation of a muscle after a lower motor neuron lesion within what time frame is likely to save the muscle and allow regain of control?
3 months
Explain neurogenic muscular atrophy:
Muscle death after a lesion to the innervating nerve (lower motor neuron lesion)
How can you distinguish between unaffected muscle and atrophic muscle in a histology slide?
Atrophic fibers will be much smaller and more angulated, with an increase in nuclei.
How can the length of the sarcomere of a muscle fiber be increased?
Via sustained stretching, such as yoga/pilates
What causes the decrease in length of a sarcomere within a muscle fiber?
Limb immobilisation, ie in plaster.
Why are muscle end plates slightly invaginated?
To increase the surface area, to increase the maximum number of neurotransmitter receptors.
Each muscle is innervated by how many motor neurons?
1 motor neuron innervates each muscle
How can 1 motor neuron innervate multiple fibers within 1 muscle?
A motor neuron commonly has multiple end plates, each innervating different fibers within the same muscle.
What neurotransmitter is released into neuromuscular junctions?
Acetylcholine
What receptor does acetylcholine bind to on the post-synaptic membrane of a neuromuscular junction?
Nicotinic Ach Receptor (NAchR)
Opening of what pre-synaptic channels causes the release of Ach into a neuromuscular synaptic cleft?
Voltage-gated Ca2+ channels
What happens to Acetylcholine in the post-synaptic membrane of a neuromuscular junction?
It is terminated by Acetylcholinesterase, and the products diffuse back across the synaptic cleft, taken up by thepre-synaptic membrane (re-used)
What proportion of NAchR need to be occupied to achieve a full sustained muscle contraction?
~25%
What is Myasthenia Gravis?
Rare autoimmune disease causing muscle weakness without atrophy. Caused by destruction of NAchR by IgG antibodies.
How do IgG antibodies affect the motor end plate in myasthenia gravis?
- Destroys NAchR’s
- Reduces invaginations of the sarcolemma, reducing surface area
What causes the sudden falling without fatigue of the muscles, in Myasthenia Gravis?
Due to the decreased number of NAchR’s, when the amount of Ach released from motor neuron drops, not enough NAchR’s are occupied to achieve a full sustained muscle contraction.
What happens to the amount of Ach released from the motor neuron over time?
Large initial peak, then drops quickly
What are the 3 primary signs of Myasthenia Gravis?
1) Drooping of upper eyelids
2) Double vision
3) Sudden falling without fatigue of muscles
What can cause symptoms of Myasthenia Gravis to worsen (short-term)?
- Poor general health
- Emotions
- Fatigue
What are the 4 treatments given to relieve Myasthenia Gravis symptoms?
1) Acetylcholinesterase inhibitors
2) Immune suppressants
3) Plasmapheresis
4) Thymectomy
Why does plasmapheresis relieve the symptoms of Myasthenia Gravis?
- Myasthenia Gravis is caused by autoimmune antibodies,
- Antibodies are carried in the blood plasma,
- Removal of plasma containing autoimmune antibodies
- Replaced with ‘good’ plasma, or plasma substitute
Why does a thymectomy often relieve the symptoms of Myasthenia Gravis?
- The Thymus gland helps protect the body against autoimmunity
- Patients suffering from MG often have a benign tumour of the thymus gland
- When removed, can alleviate symptoms
Name the 6 main types of Muscular Dystrophy:
1) Duchenne (and Becker)
2) Emery-Dreifuss
3) limb girdle
4) facioscapulohumeral
5) distal
6) occulopharyngeal
What muscles does Duchenne and Becker muscular dystrophy affect?
At first - upper arms/legs and pelvis
Later - All voluntary muscles
What muscles does Emery-Dreifuss muscular dystrophy affect?
Upper arms and shin muscles
What muscles does limb girdle muscular dystrophy affect?
Shoulder girdle and pelvic girdle muscles
What muscles does facioscapulohumeral muscular dystrophy affect?
Facial, shoulder and upper arm muscles
What muscles does distal muscular dystrophy affect?
Lower arm/leg muscles
What muscles does occulopharyngeal muscular dystrophy affect?
Eyelids and throat muscles
What is the difference between Duchenne- and Becker-type muscular dystrophies?
Duchenne-type has earlier onset and quickly progesses compared to Becker-type
Why does the lack of dystrophin cause the symptoms of Duchenne muscular dystrophy?
- Dystrophin links the sarcolemma and the actin/myosin fibres
- When lost, the muscle fibres tear apart on contraction
- Progressive atrophy of muscles
Why is Duchenne muscular dystrophy progressive?
It causes the muscles to tear themselves apart on contraction, so the more the muscles are contracted, the worse the symptoms and muscle atrophy
Why can elevated serum creatine kinase levels be indicative of muscular dystrophy?
- Muscular dystrophy is characterised by muscle destruction and atrophy,
- This causes muscle cell contents to leak out into blood
- Creatine kinase is released into serum, and easily tested for
What happens to the muscle after it has been destroyed in a patient with a type of muscular dystrophy?
The muscle fibres are replaced with fat and connective tissue
What is the typical presentation which leads to a diagnosis of Duchenne muscular dystrophy?
- Young male
- Aged below 6 yrs
- Late motor milestones
- Inability to run
- Fatigue
- Climbing up legs to stand up (Gower’s sign)
What is the initial investigation when Duchenne muscular dystrophy is suspected?
Serum creatine kinase levels, if elevated, supports possible diagnosis of DMD.
Why is swelling/hypertrophy a common symptom in patients with a muscular dystrophy?
This is pseudohypertrophy, in which the muscle fibres are being replaced with fat and connective tissue
What is the common management given to prolong independent mobility in Duchenne muscular dystrophy sufferers?
Corticosteroid therapy (Prednisolone), tends to slow rate of muscle damage.
Why is it unnecessary to give corticosteroids to a Duchenne muscular dystrophy sufferer when they are dependant on a wheelchair?
Corticosteroids are only given to DMD sufferers to prolong independent mobility. When this is lost, it is unnecessary to take corticosteroids.
What is the difference between myopathies and denervation?
Myopathies are caused by disease of the muscle, whereas denervation is caused by a disease of the nerves innervating the muscles.
What is the main risk factor for Duchenne muscular dystrophy, and why?
Family history of DMD, as it is an inherited disorder
What pattern of inheritance does Duchenne muscular dystrophy follow?
X-linked recessive
Which gender is most at risk of inheriting Duchenne muscular dystrophy, and why?
Male, as DMD is X-linked recessive, and males only have one X chromosome so only require 1 mutant copy to be affected, whereas females require 2 copies to be affected.
Give an example of an X-linked recessive myopathy:
Duchenne muscular dystrophy
What causes Duchenne muscular dystrophy?
It is an inherited disorder
What causes malignant hyperthermia susceptibility?
It is an inherited disorder
What (usually) triggers malignant hyperthermia episodes?
Anaesthetic agents
Why may some people with malignant hyperthermia susceptibility never know they have the condition?
Malignant hyperthermia episodes are only usually triggered by anaesthetic agents, so diagnosis cannot be made until person is exposed to anaesthesia.
What is the pathophysiology of a malignant hyperthermia episode?
- Increased CO2 production = metabolic and respiratory acidosis
- Activation of sympathetic nervous system
- Hyperkalemia
- Oedema
- Total skeletal muscle contraction = excessive heat production
= multiple organ failure, death
What process does anaesthetic agents trigger in a person susceptible to malignant hyperthermia?
Release of all Ca2+ from sarcoplasm of skeletal muscle