lecture presentation - fatigue - visualbee

8/6/2019 Lecture Presentation - Fatigue - VisualBee

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Metabolic basis of Muscular Fatigue


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Muscular fatigue

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Muscular fatigueMuscular fatigue

Inability to maintain aInability to maintain agiven exercise intensitygiven exercise intensity

or force outputor force output


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Muscular fatigue

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No one cause of fatigueNo one cause of fatigue

Multifocal phenomenonMultifocal phenomenonCentral and peripheralCentral and peripheralcomponentscomponents

No one cause of fatigueNo one cause of fatigue

Multifocal phenomenonMultifocal phenomenonCentral and peripheralCentral and peripheralcomponentscomponents

Metabolic fatigue results from:Metabolic fatigue results from:

Depletion of key metabolitesDepletion of key metaboliteswhich facilitate contractionwhich facilitate contractionAccumulation of metabolitesAccumulation of metaboliteswhich impair contractionwhich impair contraction

Metabolic fatigue results from:Metabolic fatigue results from:

Depletion of key metabolitesDepletion of key metaboliteswhich facilitate contractionwhich facilitate contractionAccumulation of metabolitesAccumulation of metaboliteswhich impair contractionwhich impair contraction


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Metabolite depletion - phosphagens

Phosphagen depletionPhosphagen depletionassociated with fatigue duringassociated with fatigue duringshort duration highshort duration high- -intensityintensityexerciseexercise

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Copyright 1997 Associated Press. All rights reserved.


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Immediate source of ATPImmediate source of ATPrephosphorylationrephosphorylation is is phosphocreatinephosphocreatine ( (PCrPCr))

CreatineCreatine kinasekinase functions so rapidly thatfunctions so rapidly that

muscular ATP affected little untilmuscular ATP affected little until PCr PCrsignificantly depletedsignificantly depletedATP andATP and PCrPCr concentrations in restingconcentrations in restingmuscle are lowmuscle are low

UtilisationUtilisation must be matched bymust be matched by

restoration otherwise stores rapidlyrestoration otherwise stores rapidlydeplete and fatigue occursdeplete and fatigue occurs


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During exercise at set work load

PCr decreases in two phases

Rapid initial decline

Slower secondary decline

Slower due to glycolysis and KC

increasing ATP production which

rephosphorylates PCr

Both initial decline and extent of final

decrease related to relative exercise

intensityAdapted from: Brooks GA & Fahey TD. (1985) Exercise Physiology:Human Bioenergetics and its Applications. New York: MacMillan.

p705



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ATP declines initially duringATP declines initially duringonset of exercise, but wellonset of exercise, but wellmaintained during steadymaintained during steady- -state exercisestate exercise

ATP hydrolysis buffered by PCrATP hydrolysis buffered by PCr

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Adapted from: Brooks GA & Fahey TD. (1985) Exercise Physiology: Human Bioenergetics and its Applications.New York: MacMillan. p705


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Fatigue coincides with PCr

depletion

Once PCr stores depleted ATP

concentration falls

Associated with fatigue during

short duration, high intensity

exerciseAdapted from: Sahlin K. (1986) Metabolic changes limiting muscle

performance. In: B Saltin (Ed) Biochemistry of Exercise VI.Champaign: Human Kinetics. p334



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Formation of ATP from PCrFormation of ATP from PCrhydrolysis consumes Hhydrolysis consumes H ++

Important buffering effectImportant buffering effectduring high intensity exerciseduring high intensity exercise

ADP + PCr + H+ m ATP + Cr


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Metabolite depletion - glycogen

Glycogen depletionGlycogen depletionassociated with fatigueassociated with fatigueduring prolongedduring prolongedsubmaximal exercisesubmaximal exercise

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SlowSlow--twitchtwitch fibresfibres become glycogen depletedbecome glycogen depletedfirst, followed by fastfirst, followed by fast- -twitchtwitch

Same pattern occurs during high and lowSame pattern occurs during high and lowintensity exercise due tointensity exercise due to Henneman sHenneman s sizesizeprincipleprinciple

Rate of depletion accelerated during highRate of depletion accelerated during highintensity exerciseintensity exercise

Possible to fatigue due to glycogen depletionPossible to fatigue due to glycogen depletionfrom specific musclefrom specific muscle fibresfibres when glycogenwhen glycogen

remains in otherremains in other fibresfibresLactate shuttle offsets this effectLactate shuttle offsets this effect


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Liver releases glucose to offsetLiver releases glucose to offsetreduction in muscle glycogenreduction in muscle glycogen

When liver and muscle glycogenWhen liver and muscle glycogendepleted acetyl CoA formed fromdepleted acetyl CoA formed from

--oxidationoxidation

glucose derived from gluconeogenesisglucose derived from gluconeogenesis

This slows formation of acetyl CoA (and ATP) soThis slows formation of acetyl CoA (and ATP) sofatigue occursfatigue occurs

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Metabolite accumulation - lactate

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During moderateDuring moderate- -high intensity exercise lactic acidhigh intensity exercise lactic acidaccumulates within the active muscles and bloodaccumulates within the active muscles and bloodDuring moderateDuring moderate- -high intensity exercise lactic acidhigh intensity exercise lactic acidaccumulates within the active muscles and bloodaccumulates within the active muscles and blood

Lactic acid 99.5% dissociated at physiological pHLactic acid 99.5% dissociated at physiological pH

Lactic acid accumulation associated with fatigueLactic acid accumulation associated with fatigueLactic acid accumulation associated with fatigueLactic acid accumulation associated with fatigue

Lactate ion involved in fatigueLactate ion involved in fatigue

Mechanism not knownMechanism not knownHH++ ion involved in fatigueion involved in fatigue

Number of possible mechanismsNumber of possible mechanisms


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HH++ ion may contribute to fatigue via:ion may contribute to fatigue via:Rapid depletion of PCr storesRapid depletion of PCr stores

HH++ ion involved in CK reaction and will displace reactionion involved in CK reaction and will displace reactionto favour PCr breakdownto favour PCr breakdown

ADP + PCr + H + m ATP + Cr

Inhibition of PFK (widely accepted)Inhibition of PFK (widely accepted)HH++ shown to inhibit PFK in vitroshown to inhibit PFK in vitro

In vivo, increases in AMP, ADP and F 6In vivo, increases in AMP, ADP and F 6- -P overcome thisP overcome thisinhibition so that glycolytic rate is retainedinhibition so that glycolytic rate is retained

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H+ ion may contribute to fatigue via:

Displacement of Ca 2+ from binding with troponin C

Failure to form cross-bridges and develop tension

Stimulation of pain receptors within muscle

Negative feedback mechanism (protective effect)?

Inhibition of triacylglycerol lipase activity

Reduced lipolysis will increase reliance on CHO as

fuel, leading to earlier glycogen depletion

Adapted from: Tortora GJ & Grabowski SR. (2000)Principles of Anatomy and Physiology (9th Ed). New

York: Wiley. p279



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Recent evidence suggests that

intracellular acidosis may actually protect

against fatigue by enhancing the ability of

the T-tubule system to carry action

potentials to the sarcoplasmic reticulum

K+ accumulation in T-tubules during

muscle contraction reduces excitability of

T-tubules (due to inactivation of some

voltage gated channels)

Reduces ability to carry electrical signals

to sarcoplasmic reticulum

Reduced release of calcium from SR

results in fewer cross-bridges being

formed and loss of force

Adapted from: Pedersen et al. Intracellular acidosis enhances the excitability of working muscle. Science 305:1144-1147, 2004.



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Metabolite accumulation - calcium

CaCa2+2+ released from sarcoplasmicreleased from sarcoplasmicreticulum may enter mitochondriareticulum may enter mitochondria

Increased CaIncreased Ca 2+2+ in mitochondrialin mitochondrial

matrix would reduce electricalmatrix would reduce electricalgradient across inner membranegradient across inner membraneWould reduce HWould reduce H ++ flow through ATPflow through ATPsynthasesynthase

Reduced ATP productionReduced ATP production

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From: Matthews, CK & van Holde KE (1990) Biochemistry. Redwood City:Benjamin Cummings p.526.

lecture presentation - fatigue - visualbee

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