Introduction to pathophysiology of skeletal muscle Flashcards Preview

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How can you describe skeletal muscle?



How is skeletal muscle plastic?

Adapts to changes in functional demand


What does skeletal muscle respond to during endurance exercise?

Total contractile activity


What does skeletal muscle respond to during resistance training?

Loading and stretch


List some adaptations of skeletal muscle that makes it plastic

Structural eg. size and capillarisation
Contractile properties eg. fibre type transitions


When does adaptability occur?

From embryogenesis into maturity


Describe the structural adaptation of skeletal muscle

Total number of muscle fibres fixed at birth


Give the name of the process of muscle growth



Describe hypertrophy

Synthesis of myofilaments
Addition of sarcomeres
Satellite cell activation
Angiogenesis and vascularisation


How much do some muscles enlarge by?



Give some examples of endurance exercise

distance running, cycling or swimming
(low force, high contractile frequencies)


What can endurance exercise cause in the muscle?

Increased fibre diameter
Increased blood supply, increased oxidative capacity
Increased mitochondrial content
Increase in oxidative enzymes
Slower fibres


What transformation of fibre type occurs with endurance exercise?

Gradual transformation of type IIX to type IIA


What transformation of fibre type occurs with non-endurance exercise?

Conversion of type IIA to type IIX


What does non-endurance exercise result in?

Increase type IIX fibre size due to increased number of sarcomeres and myofilaments
Results in larger muscles (bulk) and an increase in power


What is ice used for?

To reduce swelling by reducing perfusion
After an acute injury such as a sprain
After exercise in overuse injury


What is heat used for?

To relax and loosen tissues
Use before activities that irritate chronic injuries such as strain
Increases blood flow


What class of drugs is aspirin?

Non steroidal anti inflammatory


What does aspirin do?

Reduces pain and inflammation


Where is aspirin used for in musculoskeletal conditions?

Chronic diseases - osteoarthritis
Sports injuries - combined with ice often after exercise


How does aspirin work?

Inhibits COX
Reduces prostaglandin synthesis
Part of arachidonic acid pathway


What adverse effects do prostaglandins and arachidonic acids have?

Stomach bleeding
Gastric ulcers


List the anabolic effects of testosterone

Increases protein synthesis
Decreases catabolism (by opposing cortisol & glucocorticoids)
Reduces fat: increase BMR, increase differentiation to muscle (rather than fat cells)


Why are anabolic steroids abused?

used to increase muscle size and strength


Give the side effects of anabolic steroid abuse

large doses required – leads to damaging
side effects (kidney, liver, heart, mood

male – testes atrophy, sterility, baldness

female – breast/uterus atrophy, menstrual
changes, facial hair, deepening of voice


What does space flight do to muscles?

Decreased weight bearing
Transition of type I fibres to type IIA/X fibres
Decreased relative muscle mass - all muscles undergo some atrophy - predominately weight bearing muscles


What does bed rest do to muscles?

transition of type I fibres to type IIA

weight-bearing muscle atrophy
- decreased muscle protein synthesis
- myofibrillar breakdown
- Decreased strength (due to decreased size)
- loss of type I fibres


How do you treat the effects of bed rest?

treat by resuming minor activity early. Add physiotherapy to prevent contractures.


What is contracture?

Shortening of muscle


How does contracture occur?

if limb immobilised for long periods:

process of growth is reversed
sarcomeres are removed in series from myofibrils


How can contracture be prevented?

patients with paralysed limbs must have physical therapy to prevent contractures occurring


What word is used to describe the cellular structure of skeletal muscle



Describe the development of skeletal muscle cells

They develop as myoblasts
Which are mononucleate
Then the myoblasts fuse

The nuclei are peripheral

The multinucleate cells do not divide
Mitosis with multiple nuclei usually impossible


How are skeletal muscles enlarged?

Fibre enlargement
Increased vascularisation


Describe muscle regeneration

During inflammation and degeneration of damaged muscle tissue

previous quiescent myogenic cells, called satellite cells, are activated
These proliferate, differentiate and fuse onto extant fibres
They contribute to forming multinucleate myofibers


What are myosatellite cells?

Progenitor cells in muscle
Also called “satellite cells”
NOT related glial satellite cells
Essential for regeneration & growth
Most are quiescent
Activated by mechanical strain
Activation —> proliferation & differentiation


What is myalgia?

Muscle pain


Give some causes of myalgia

Injury, overuse, infections, auto-immune


What can myalgia be associated with?



What is myopathy?

Muscular weakness due to muscular muscle fibre dysfunction
Cf. neuropathy & neurogenic disorders
Failure to contract cause possibly muscle or nerve
Systemic vs. familial


What are dystrophies?

familial, progressive
Stuck in degeneration-regeneration cycle
Eventually regenerative ability is lost


What is paresis?

weakness of voluntary movement, or
partial loss of voluntary movement or
impaired movement

Usually referring to a limb

From Greek “to let fall”


What are fasciculations?

involuntary visible twitches in single motor units (neurogenic)


When do fasciculations occur?

commonly occur in lower motor neuron diseases such as damage to anterior horn cell bodies characteristic of ALS or polio


How do fasciculations appear clinically?

clinically appear as brief ripples under the skin


What are fibrillations?

involuntary spontaneous contractions of individual muscle fibres (myogenic) invisible to the eye but identified by electromyography


What is rhabdomyolysis?

Rapid breakdown of skeletal muscle


What is rhabdomyolysis a risk for?

Risk of kidney failure
Cellular proteins (esp myoglobin) released into blood can “clog” renal glomeruli
Urine is “tea coloured”, no urine produced 12 hours after injury
Leads to electrolyte changes: hyperkalaemia


How is rhabdomyolysis treated?

Intravenous fluids (to treat shock)
possibly haemodialysis, etc


List some causes of rhabdomyolysis

Trauma: Crush injury
adverse effects of: statins or fibrates
Ischaemia to the skeletal muscle
Compartment syndrome, thrombosis


Give some symptoms and signs of rhabdomyolysis

muscle pains
vomiting and confusion
Dark urine


What is Creatine Phosphokinase (CK/CPK) and what is it used for clinically?

The enzyme

distinct forms of CPK found in different tissues

skeletal muscle CPK isoform is CK-MM
cardiac muscle CPK isoform is CK-MB

when tissue damaged and cells lyse there is a release of tissue specific CK from cells into blood
Elevations in CK-MM occur after skeletal muscle trauma or necrosis
muscular dystrophies, polymyositis and rhabdomyolysis
Test = “Total CK” (CK-MM is not a clinical test)


What is myoglobin and how is it diagnostic?

“Buffers O2”
Protein + Haem group
“tea coloured”
In plasma indicates rhabdomyolysis or MI
Can lead to renal failure
Urine tested for myoglobin

Diagnostic: Hyperkalaemia
When muscle cells lyse
They release K+
This increases serum K+

Nb: decreased serum K = cause of rhabdo,
increased K = result of rhabdo


What is myasthenia gravis?

progressive muscle weakness and fatigability
Often starts with eye muscles

Caused by depletion of nAChR

arises as the immune system inappropriately produces auto-antibodies against nAChR

less depolarisation of muscle fibres
many fibres do not reach threshold

repeated stimulation leads to neuromuscular fatigue

symptoms include ptosis, diplopia,
with weakness in eyelid and extraocular muscles

proximal muscle weakness


Describe different treatment options for MG

AChE inhibitors
Increase ACh activity at NMJ. ACh released from nerve terminals into synapse not rapidly catabolised but can bind to the remaining AChRs for longer time

Edrophonium (a/k/a tensilon): short-lived AChE inhibitor for diagnosis, temporarily improves symptoms eg ptosis

Other category of treatment is directed at immune system

Thymectomy – reduces symptoms in 70% of patients. Exact mechanism unknown. Rebalance immune system?

use of immunosuppressive drugs e.g. corticosteroids

plasmapheresis = removal of anti AChR antibodies from blood stream


What is spinal muscular atrophy?

a/k/a Floppy Baby Syndrome
One of most common genetic causes of infant death
Severity and time of onset can vary greatly

death of lower motor neurons in anterior horn of spine
Muscle atrophy —> hypotonia & muscle weakness
Via apoptosis
Fibre type grouping
Sensory system is spared (b/c not in anterior horn)


What causes spinal muscular atrophy?

Caused by genetic defect
SMN1 gene
Required for survival of anterior horn neurons
Autosomal recessive
Other genes cause similar syndromes


Describe fibre type grouping

During spinal muscular atrophy
Cycles of denervation are followed by collateral reinnervation
surviving axons innervate surrounding fibres
resulting in fibre type grouping
In healthy muscles, motor units are intermingled. During reinnervation, nearby surviving neurons re-innervate the denervated fibres, resulting in clusters


What is malignant hyperthermia?

Genetic (rare) susceptibility to gas anaesthetics
Eg sevoflurane

Mutation in RyR means gas anaesthetic - Ca2+ release
Autosomal Dominant
Channel is susceptible if any of subunits are

Result: SERCA works too hard (to pump Ca back into SR)

Increased O2 consumption, increased CO2, acidosis, tachypnea, muscles overheat, the body overheats, muscles are damaged (rhabdomyolysis), hyperkalaemia, muscles become rigid

Muscle cells open and leak their contents

Plasma CK-MM increases

Kidney failure possible: urine red from myoglobin

dantrolene sodium can stop the abnormal calcium release
Inhibits ryanodine receptor


Describe muscular dystrophies

group of inherited disorders
severe and progressive wasting of muscle
muscle weakness
Due to myopathy, not neuropathy
waddling gate
cardiorespiratory muscle involvement


What is duchenne muscular dystrophy?

x-linked disease
affects 1:3500 live male births
one third of cases arise spontaneously
progressive loss of muscle tissue
replaced by fibrofatty connective tissue
Mutation: gene for dystrophin protein