L2 - Pathophysiol of skeletal muscle

Question 1

PLASTICITY OF SKEL MUSCLE

i) what does muscle adapt in response to?
ii) name two types of exercise that can cause change and what the muscle responds to in each
iii) what are the two types of adaptation that muscles undergo? give an eg of each
iv) over what time period can adaptation take place?

Answer 1

i) changes in func demand

ii) endurance exercise > response to total contractile activity
- resistance training > response to loading and stretch

iii) structural > inc in size/capillarisation
- contractile properties > fibre type transition

iv) can take place from embryogenesis into maturity

Question 2

STRUCTURAL ADAPTATION OF MUSCLE

i) are total number of muscle fibres in a single muscle fixed at birth or changed through life?
ii) what is muscle growth aka?
iii) name four things associated with muscle growth
iv) what % can some muscles enlarge by due to exercise?
v) what is a muscle fibre?

Answer 2

i) fixed at birth
ii) muscle growth = hypertrophy

iii) synthesis of myofilaments
- addition of sarcomeres
- satellite cell activation
- angiogenesis/vascularisation

iv) some muscles can enlarge by 15-50%
v) a long multinucleated cell

Question 3

EFFECT OF ENDURANCE EXERCISE

i) give three examples of this type of exercise
ii) what level of force and contractile frequency are seen?
iii) how does fibre diameter change? is this dramatic or slight?
iv) how does blood supply change? what effect does this have on oxidative capacity? how will expression of oxidative enzymes therefore change?
v) do fibres become faster or slower? which fibre is there a gradual transition from and to?

Answer 3

i) distance running, cycling and swimming
ii) low force and high contractile frequency
iii) fibre diameter has a slight increase

iv) big increase in blood supply
- increase in oxidative capacity (ability to use O2 and create energy)
- therefore increased expression of oxidative enzymes

v) fibres become slower
- transition from type IIX to type IIA

Question 4

NON ENDURANCE EXERCISE

i) what type do fibres convert from and to?
ii) how does muscle force and strength change with this type of exercise?
iii) name two things that increase in number? what are these two things responsible for?
iv) what does this ultimately result in? (2)

Answer 4

i) from type IIA to type IIX
ii) greater muscle force and strength

iii) increase in numbers of sarcomeres and myofilaments
- responsible for increase in type IIX fibre size

iv) ultimately results in larger muscle bulk and increased power

Question 5

ICE AND HEAT

i) in what type of injury is ice used? (name and timing)
ii) how does ice impact on swelling? how does it do this?
iii) in what type of injury is heat used? (name and timing)
iv) what effect does heat have? what is the desired effect of using heat?
v) would ice or heat be given in a) after exercise in overuse injury, b) before activity to prevent irritation of chronic injury

Answer 5

i) ice is used after an acute injury = sprain
ii) ice reduces swelling by reducing perfusion
iii) heat is used before activity to minimise further damage in a sprain

iv) heat increases perfusion locally
- to relax and loosen tissues

v) post exercise in overuse = ice
- before activity to prevent further irritation = heat

Question 6

ASPIRIN AND MSK PAIN

i) what type of drug is aspirin? name another drug that belongs to this class? name two things aspirin reduces
ii) give two types of MSK pain that aspirin may be used in with an example of each
iii) by what mechanism does aspirin work? (what does it inhibit and what does this reduce synthesis of?) what pathway is this a part of?
iv) what is the main side effect of chronic aspirin use? (2)

Answer 6

i) aspirin is an NSAID - so is ibuprofen
- aspirin reduces pain and inflammation

ii) aspirin used in chronic disease eg OA and sports injury (combined with ice after exercise)

iii) aspirin inhibits COX
- reduces synthesis of prostaglandin
- part of arachadonic acid pathway

iv) main SE - GI problems eg stomach bleeding and ulcers

Question 7

TESTOSTERONE

i) what type of effect does testosterone have? what does it increase and what does it decrease and how does it do this?
ii) how does testos treatment impact on fat? give two further things it increases
iii) what may anabolic steroids be abused for? (2) do you need a large or small dose? name three things that may suffer side effects?
iv) give two side effects seen in males and two seen in females

Answer 7

i) anabolic effect
- increases protein synthesis
- decreases catabolism by opposing cortisol and GCs

ii) reduces fat
- increases BMR
- increases differentiation to muscle rather than fat

iii) abused to increase muscle size and strength
- need large doses to get effect
- SEs in kidney, liver, heart, mood change

iv) males - testes atrophy and sterility, balding
females - breast/uterus atrophy, menstrual change, facial hair

Question 8

EFFECT OF SPACE FLIGHT

i) what type of fibres are lost and what do they become?
ii) how does relative muscle mass change? which muscles does this particularly affect? give two examples

Answer 8

i) loss of slow fibres (type I) move to fast fibres (type IIA/X)

ii) decrease in relative muscle mass
- partic affects weight bearing muscles eg back musc and quad

Question 9

EFFECT OF BED REST

i) what type of fibres transition? what do they become?
ii) name four things that are associated with weight bearing muscle atrophy
iii) how can this be treated?
iv) which healthcare worker can be employed? what can they prevent?

Answer 9

i) transition from type I to type IIA

ii) weight bearing atrophy due to decrease in musc prot syn
- myofibrillar break down
- decreased strength due to decreased size
- loss of type I fibres

iii) treat by resuming minor activity early on
iv) physiotherapist - to prevent contractures (musc permanently smaller)

Question 10

FIBRE TYPE SUMMARY

i) which type of fibres contract slowly?
ii) which type of fibres have lots of mitochondria and high capillary density? what does this allow?
iii) name three types of fast fibres
iv) do fast fibres have lots of mitochondria and capillary density?

Answer 10

i) type I contract slow
ii) slow type I fibres have lots of mito and high cap density which allows resistance to fatigue
iii) fast fibres - Type IIA/X/b
iv) fast fibres dont have lots of mito and low cap density

Question 11

CONTRACTURE

i) when does this happen?
ii) what happens to the process of growth?
iii) what happens to sarcomeres? what does this result in?
iv) what must patients with paralysed limbs have to prevent contractures occuring? what happens if they dont?

Answer 11

i) if limb is immobilised for long periods
ii) process of growth is reversed

iii) sarcomeres are removed in series from myofibrils
- results in shortening of the muscle = contracture

iv) paralysed limb > physical therapy to prev contracture
- if no therapy their limb will stay in the contracted position

Question 12

SKELETAL MUSCLE CELLS

i) which cells do they develop from? are these mono or multinucleate?
ii) what then happens for them to become a single long cell? what location are nuclei found in these cells?
iii) do multinucleate cells divide? why?
iv) name two ways which skeletal muscle enlarge

Answer 12

i) develop from myoblasts = mononucleate

ii) myoblasts fuse > single long multinuc cell
- nuclei are found peripherally

iii) multinuc cells dont divide as the nuc cant all organise to divide at the same time
iv) skel muscles enlarge by fibre enlargement and increased vascularisation

Question 13

MUSCLE REGENERATION

i) name two occasions that this occurs in? what activity can damage a muscle fibre?
ii) what type of cells are present in a resting myofibre (before injury)
iii) what is released when a muscle cell is injured? what cells allow repair?
iv) how to satellite cells aid muscle regeneration? (3) what do they contribute to?

Answer 13

i) inflammation and degeneration of damaged muscle tissue
- exercise can damage a muscle fibre

ii) quiescent satellite cells are pres in a resting myofibre

iii) on injury > release growth factor that downregulates caveolin 1 expression
- myogenic precursor cells allow repair

iv) satellite cells prolif, differentiate and fuse onto injured fibres
- contribute to forming multinuc myofibres

Question 14

MYOSATELLITE CELLS

i) what are they aka? what do they act as?
ii) what are they essential for?
iii) what state are most of these cells in? what causes them to be activated?
iv) what happens when they are activated? (3)

Answer 14

i) aka satellite cells
- act as progenitor cells in the muscle

ii) essential for regeneration and growth

iii) most cells are quiescent
- mechanical strain activates them

iv) once activated > prolif/differen/join the func muscle

Question 15

MYALGIA

i) what is it?
ii) give four causes
iii) what can it be associated with?

Answer 15

i) muscle pain
ii) injury, overuse, infections, auto-immune
iii) can be assoc with rhabdomyolysis (destruc of muscle)

Question 16

MYOPATHY

i) what is it? what is it due to? what does it have to be distinguished from?
ii) what is dystrophy? what cycle is the muscle stuck in? what does this eventually lead to?

Answer 16

i) muscular weakness/disease due to muscle fibre dysfunction
- have to eliminate a neuronal cause (neuropathy)

ii) dystrophy is incorrect musc nourishment/growth
- stuck in degen/regen cycle
- eventually regenerative capacity is lost > permanent damage

Question 17

PARESIS

i) name three things that are classed as paresis
ii) which area of the body is it usually referring to?

Answer 17

i) weakness of voluntary movement
- partial loss of voluntary movement
- impaired movement

ii) usually refers to a limb

Question 18

INVOLUNTARY TWITCHES

i) what are fasiculations? where do they ocur?
ii) are fasiculations neurogenic or myogenic? which class of diseases do they usually occur in? give an example
iii) how do fasiculations appear clinically?
iv) what are fibrillations? what structures do they occur in?
v) are fibrillations neurogenic or myogenic? can they be seen by the naked eye? how can they be identified?

Answer 18

i) fasiculations are involuntary visible twitches that occur in single motor units

ii) fasiculations are neurogenic
- usually occur in lower motor neuron disease eg damange to anterior horn cell bodies in ALS/polio

iii) clinically appear as visible brief ripples under the skin
iv) fibrillations are involuntary spontaneous contractions of individual muscle fibres

v) fibrillations are myogenic and cant be seen by naked eye
- can be identified by electromyography (electrodes on skin)

Question 19

RHABDOMYOLYSIS

i) what is it? what type of muscle is affected?
ii) what does it increase the risk of? why?
iii) how may the urine appear? what may happen 12hrs post injury?
iv) what electrolyte changes may be seen?
v) give two treatments

Answer 19

i) rapid breakdown of skeletal muscle (not cardiac)

ii) increases risk of kidney failure
- due to release of cellular proteins (myoglobin) which can clog the renal glomeruli

iii) urine can appear tea coloured and there may be no urine produced 12 hours post injury
iv) results in hyperkalemia (K+ leaks out of cells as they lyse)
v) IV fluid to treat shock and possible haemodialysis

Question 20

CAUSES OF RHABDOMYOLYSIS

i) what is the principle cause of RML?
ii) give two drugs that can cause it
iii) give two other causes
iv) give three symptoms/signs

Answer 20

i) trauma > crush injury
ii) statins and fibrates
iii) hyperthermia and ischaemia to skel muscle
iv) muscle pain, vomiting/confusion, dark urine

Question 21

RML DIAGNOSIS - CREATINE PHOSPHOKINASE

i) which form of CPK is found in skeletal muscle?
ii) when is CPK released from cells to the blood? which two events can cause this
iii) name three instances CK-MM may be raised in
iv) what is the clinical test for CPK?

Answer 21

i) CK-MM

ii) CPK is released from cells when the tissue is damaged and the cels lyse > release of tissue spec CK from cells to blood
- can be caused post skeletal muscle trauma and necrosis

iii) raised CK-MM in muscular dystrophy, polymyositis, rhabdomyolysis
iv) clinical test is total CK

Question 22

RML DIAGNOSIS - MYOGLOBIN

i) where may myoglobin be detected in RML?
ii) what does myoglobin in the plasma indicate? (2) what can it lead to?
iii) what potassium levels are a result of RML? why? what potassium levels are a possible cause of RML?
iv) what colour may urine be in RML?

Answer 22

i) urine

ii) myoglobin in the plasma indicates RML or MI
- can lead to renal failure

iii) hyperkalemia is a result of RML
- muscle cells lyse and release K+ > increases serum K+
- hypokalemia can be a cause of RML

iv) urine may be tea coloured

Question 23

RIGOR MORTIS

i) depletion of what molecule causes it? what does this not allow? what does this result in?
ii) which formation does myosin remain in? what does this cause?
iii) when does rigor mortis start? when does it end? why does it end?

Answer 23

i) ATP depeleted after death
- does not allow muscle to resequester calcium into the SR
- results in high cytosolic calcium > allows crossbridge cycle contraction

ii) myosin remains bound to actin which causes permanent contraction
iii) RM starts at 3hrs post death and ends around 3 days post death due to muscle tissue degradation

Question 24

MYASTHENIA GRAVIS

i) what is it? what muscles does it usually start in?
ii) what causes it? what may responsible for this?
iii) name two symptoms that may be seen first? which two groups of muscles are implicated here
iv) what happens to level of depolarisation of muscle fibres? what does this lead to?
v) what can repeated stimulation of muscles cause? what symptom is this seen in
vi) which group of muscles do symptoms start in?

Answer 24

i) progressive muscle weakness and fatigue
- usually starts in eye muscles

ii) caused by depletion of nicotinic Ach receptors
- arises as the immune system inappropriately produces auto antibodies against the nACHR

iii) see ptosis and diplopia > eyelid and extraocular muscles

iv) there is less depolarisation of muscle fibres
- leads to many fibres not reaching threshold > less activity

v) repeated stim can cause NM fatigue > seen in ptosis
vi) proximal muscle weakness

Question 25

MYASTHENIA GRAVIS - DX AND TX

i) what is the main class of drugs used to treat MG? give an example
ii) what is the mechanism of action of these drugs?
iii) name another drug that may be used and temporarily improves symptoms
iv) what is the other category of treatment?
v) give three treatments that fall into this category and explain each

Answer 25

i) Achesterase inhibitors eg pyridostingmine
ii) increase activity of Ach at the NMJ - Ach is not broken down so can bind the remaining AchRs for a longer time
iii) edrophonium - short lived ACE inhibitor
iv) other tx - directed at the immune system

v) thymectomy - reduces symp in 70% pts
- immunosupressive drugs eg corticosteroids
- plasmapheresis - removal of anti AchR antibodies from blood

Question 26

SPINAL MUSCULAR ATROPHY

i) what is it one of the most common genetic causes of?
ii) which motor neurons are implicated? where are these located? name two things this causes? what type of cell death occurs?
iii) which division of the nervous system is spared?
iv) what causes it? is it auto dom or recessive?

Answer 26

i) one of the most common genetic causes of infant death

ii) implicates lower motor neurons in the anterior horn of the spinal cord
- causes muscle atrophy > hypotonia and muscle weakness
- fibre type grouping
- muscles destroyed via apoptosis

iii) sensory system is spared as it is not in the anterior horn

iv) caused by a genetic defect in SMN1 gene
- autosomal recessive

Question 27

FIBRE TYPE GROUPING

i) what is it and when does it occur?
ii) how are motor units organised in healthy muscle? how are they organised in fibre type grouping? explain this
iii) how can fibre type grouping be tested for?
iv) which picture depicts fibre type grouping?
v) which motor neurons are affected to cause this

Answer 27

i) cycles of denervation followed by collateral renervation
- occurs during spinal muscular atrophy

ii) in healthy muscle - motor units are intermingled
- fibre type grouping - motor units are arranged in clusters
due to denervation then renervation by surrounding fibres

iii) test by muscle biopsy
iv) B shows FTG
v) due to lower motor neuron pathology

Question 28

MALIGNANT HYPERTHERMIA

i) what is it?
ii) where is there a mutation? what does this lead to? is it auto dom or recessive? what effect does this have on SERCA?
iii) name five subsequent effects? name two things that can happen to the muscle
iv) which plasma marker will be increased? which organ is susceptible to failure?
v) what can be given to counteract the effect? how does this work?

Answer 28

i) genetic (rare) susceptibility to gas anaesthetic eg sevoflurane

ii) mutation in ryanodine receptor
- leads to lots of calcium release into the cytosol
- auto dominant
- SERCA works hard to try and pump the calcium back into SR

iii) high oxygen consumption, high co2, acidosis, tachypnea, muscle and body overheats, rhabdomyolysis > hyperkalemia
- rhabdomyolysis and muscles become rigid

iv) increase in plasma CK-MM
- kidney failure is possible > red from myoglobin

v) give dantrolene sodium which stops abnormal calcium release by inhibiting ryanodine receptor

Question 29

MUSCULAR DYSTROPHIES

i) what are they?
ii) what are they due to
iii) give three characteristics

Answer 29

i) group of inherited disorders that involve severe and progressive muscle wasting
ii) due to myopathy (not neuropathy)
iii) waddling gate, contracture and cardioresp involvement which can be fatal

Question 30

DUCHENNE MUSCULAR DYSTROPHY

i) what type of genetic disease is it? what sex does it affect?
ii) how many live births does it affect? what proportion of cases arise spontaneously?
iii) what happens? (2)
iv) which protein in there a mutation?
v) what is a characterstic sign/posture of DMD? why does this occur?

Answer 30

i) X linked - affects males

ii) 1 in 3500 live births
- 1/3 arise spontaneously

iii) progressive loss of muscle tissue that is replaced by fibrofatty connective tissue
iv) mutation in dystrophin proteins (allows sarcomeres to maintain structure)
v) Gowers sign - crawl to stand up as glutes aren’t strong enough to power this