Session 7: Disorders of Muscle Flashcards by Nevan Senaratne

What is dystrophy?

Degeneration of tissue due to disease (genetic)

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What is myopathy?

Primary disease of the muscle

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What is atrophy?

Wasting of muscle due to underuse

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What is sarcopenia?

Wasting of muscle as a result of ageing

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What is hypertrophy?

Increase in size of an organ due to increase in volume (muscle) of its constituent cells

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Which muscle type has the greatest capacity to regenerate of all muscle types?

Smooth muscle

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Which muscle type cannot regenerate and when damaged leads to invasion via fibroblasts?

Cardiac muscle

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Which muscle relies on a population of stem cells for regeneration?

Skeletal muscle

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Cardiac muscle can undergo hypertrophy via the process known as?

Sarcomerogenesis

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Give an example of when smooth muscle undergoes hypertrophy.

Myometrium in pregnant women - becomes thicker with hypertrophy

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In skeletal muscle, contractile proteins are replaced every how many weeks?

Two weeks

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What is muscle atrophy?

Rate of destruction exceeds rate of replacement in skeletal muscle

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What is muscle hypertrophy?

If rate of replacement exceeds rate of destruction in skeletal muscle

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What changes are accompanied by muscle hypertrophy?

Increase in fibre size of muscle
Metabolic changes
Increase in blood flow

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What is exercise-induced hypertrophy?

Increase in size of muscle as a result of resistance training

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What is one adaptation of skeletal muscle after lots of exercise?

Increase in number of mitochondria

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What is one repetitive practice that leads to increased number of sarcomeres?

Frequent stretching

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What is disuse atrophy?

Prolonged inactivity leads to loss of contractile proteins, reduced fibre diameter and loss of power

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What are risk factors for disuse atrophy of skeletal muscle?

Bed rest
Limb immobilisation
Sedentary behaviour

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Disuse atrophy affects which muscles more than flexor muscles?

Extensor muscles

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What is sarcopenia?

The loss of muscle mass, strength, and function that comes with aging

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Skeletal muscle mass declines from what age?

30 years

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What is the percentage loss of skeletal muscle mass by age of 80 years?

50%

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What is a risk factor for sarcopenia?

Ageing

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Sarcopenia can be counteracted by what type of training?

Resistance training

Which type muscle fibres are decreased with ageing?

There is a **loss** of **type II fibres** with age

Muscle atrophy due to ageing is accompanied by an increase in what types of tissue?

Connective tissue and fat Using MRI scan, more subcutaneous fat and intramuscular fat

What is denervation atrophy usually due to?

Lower motor neuron lesions occurring between the spinal cord and muscle

What is denervation atrophy associated with?

Muscle weakness, loss of muscle tone (flaccidity), muscle atrophy

If cell bodies remain intact, where can severed axons undergo repair?

PNS

What is the autoimmune condition affecting neuromuscular junction?

Myasthenia Gravis

What causes Myasthenia Gravis?

Damage to end-plate acetylcholine receptors at neuromuscular junctions

What are symptoms of Myasthenia Gravis?

Ptosis, facial weakness, double vision, difficulty speaking, difficulty breathing, fatigue and sudden falling

What is the management of Myasthenia Gravis?

Avoid triggers, acetylcholinesterase inhibitors, surgery for thymus gland removal

Name two common acetylcholinesterase inhibitors used to manage Myasthenia Gravis.

**Neostigmine**, Pyridostigmine

Name one bacterial cause of blocked ACh release at the NMJ.

**Botulinum toxin** (e.g., BoNT-A) released by Clostridium botulinum

What does Clostridium botulinum cause?

Botulism, paralysis of affected muscle due to blocked ACh release at NMJ

Organophosphate Poisoning

Exposure to what is one of the most common causes of neurotoxin poisoning?

Organophosphate (OP)

What does Organophosphate poisoning lead to?

Neurotoxic effects, respiratory failure or CVS - fatal

List all six forms of muscular dystrophy.

1) Duchenne-type and Becker-type 2) Emery-Dreifuss 3) Limb girdle 4) Facioscapulohumeral 5) Distal 6) Occulopharyngeal

What causes Duchenne MD?

Mutation (deletion) in dystrophin gene leading to loss of actin-binding protein dystrophin

What is the role of dystrophin protein?

Links cytoskeleton with ECM and **stabilises sarcolemma of muscle**

What condition is associated with the loss of actin-binding protein dystrophin?

Duchenne MD

What is Becker MD?

Milder form of Duchenne's MD - deficiency in dystrophin function rather than full loss

What is Limb girdle MD?

Deficiency of sarcoglycans, important in ECM interactions

What is Congenital MD?

50% deficiency of ECM protein merosin which is a major component of the basement membrane

What is the inheritance pattern of Duchenne MD?

X-linked recessive

What mutation causes Duchenne MD?

Mutation (mainly deletions) in dystrophin gene leading to loss of actin-binding protein dystrophin

What is the onset age of Duchenne MD?

Early onset (~2-7 years)

What characteristic sign does Duchenne MD show in children?

Gower's sign

What is Gower's sign?

Difficulty rising to standing position; has to walk up legs using hands

What is the pathophysiology of Duchenne MD?

1) Loss of actin-binding protein dystrophin 2) Fragile sarcolemma means tears occur during contraction 3) Creatine phosphokinase liberated into serum 4) Impaired calcium homeostasis leading to damaged contractile fibres 5) Inflammation & necrosis 6) Pseudohypertrophy occurs

What is pseudohypertrophy?

When fat and fibrous connective tissue replace muscle, leading to an enlargement of the organ

What are the histological changes in Duchenne MD?

Increased adipose deposition, increased connective tissue deposition, atrophy of muscle fibres

What form of prenatal screening can be conducted for Duchenne MD?

In utero foetal muscle biopsy

What is one future potential promising treatment for Duchenne MD?

Gene therapy with transfected myoblasts

Name an inflammatory myopathy.

Polymyositis

Give one OTHER cause of an inflammatory myopathy.

Electrolyte imbalance (e.g., hypokalaemia, hypocalcaemia)

What can diuretic therapies lead to?

Hypokalaemia - which can cause muscle weakness

What can hypoparathyroidism lead to?

Calcium imbalance - hypocalcemia - which can cause muscle spasms

What is the most common cause of severe reaction to general anaesthesia?

Autosomal dominant mutation in RYR1 gene

What does the RYR1 gene encode?

Subtype 1 ryanodine receptor (Ca2+ release channel located in the SR)

What is the treatment for RYR-1 general anaesthesia reaction?

RYR1 antagonist, muscle relaxant - dantrolene, cooling

What is the effect of the RYR-1 severe reaction to general anaesthesia on the patient?

Exposure to anaesthetic leads to release of calcium ions, leading to muscle contraction, production of excess heat, malignant hyperthermia

What is thyrotoxicosis?

Condition caused by excessive thyroid hormones (hyperthyroidism)

What is rhabdomyolysis?

**Breakdown of skeletal muscle** caused by trauma, extreme exertion/exercise, or drug toxicity * **Myoglobin then leaks into circulation**, **damaging the kidneys**, therefore there will be **tea coloured urine** due to the myoglobin deposition in urine.

Rhabdomyolysis can occur as a rare complication of the use of what medication?

Statins

What type of stem cell will repair damaged neonatal cardiac myocytes?

Mesenchymal stem cells

What type of tissue will replace damaged adult cardiac muscle?

Dense irregular connective tissue

Fibrosis of which specific cardiac feature will lead to arrhythmias?

Sinoatrial node

What are causes of excess cortisol levels in Cushing's syndrome?

1) Long-term oral corticosteroid usage 2) Excessive release of adrenocorticotropic hormone (ACTH) from anterior pituitary

What is a serious form of paralytic illness resulting from Clostridium infection?

Botulism

What is irreversible inhibition of acetylcholinesterase resulting from exposure to pesticides?

Organophosphate poisoning

What is an X-linked recessive disease causing progressive muscle weakness?

Duchenne muscular dystrophy

What is a rare life-threatening genetic disease caused by certain anaesthetics?

Malignant hyperthermia

What is the name given to tissue damage arising as a consequence of oxygen deprivation?

Ischaemia

What cardiac protein is routinely assayed to investigate a possible myocardial infarction?

Troponin

What does dystrophin protein do?

Links cytoskeleton with ECM to stabilise the sarcolemma

What are sarcoglycans?

Trans-membrane proteins that are important in ECM interactions

What type of muscle fibres are rich in muscles that resist gravity and require bursts of movement?

Type IIa fibres

Differences in red and white muscle fibres?

Histological changes in Duchenne MD - stained for dystrophin

Increased adipose deposition Increased connective tissue deposition Atrophy of muscle fibres Note = less dystrophin in stain