Lecture Presentation - Fatigue - VisualBee
-
Upload
william-wayland -
Category
Documents
-
view
230 -
download
0
Transcript of Lecture Presentation - Fatigue - VisualBee
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
1/17
1
Metabolic basis of Muscular Fatigue
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
2/17
Muscular fatigue
2
Muscular fatigueMuscular fatigue
Inability to maintain aInability to maintain agiven exercise intensitygiven exercise intensity
or force outputor force output
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
3/17
Muscular fatigue
3
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
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
4/17
Metabolite depletion - phosphagens
Phosphagen depletionPhosphagen depletionassociated with fatigue duringassociated with fatigue duringshort duration highshort duration high- -intensityintensityexerciseexercise
4
Copyright 1997 Associated Press. All rights reserved.
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
5/17
Metabolite depletion - phosphagens
5
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
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
6/17
6
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
Metabolite depletion - phosphagens
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
7/17
Metabolite depletion - phosphagens
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
7
Adapted from: Brooks GA & Fahey TD. (1985) Exercise Physiology: Human Bioenergetics and its Applications.New York: MacMillan. p705
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
8/17
8
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
Metabolite depletion - phosphagens
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
9/17
9
Metabolite depletion - phosphagens
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
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
10/17
Metabolite depletion - glycogen
Glycogen depletionGlycogen depletionassociated with fatigueassociated with fatigueduring prolongedduring prolongedsubmaximal exercisesubmaximal exercise
10
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
11/17
Metabolite depletion - glycogen
11
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
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
12/17
Metabolite depletion - glycogen
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
12
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
13/17
Metabolite accumulation - lactate
13
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
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
14/17
Metabolite accumulation - lactate
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
14
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
15/17
15
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
Metabolite accumulation - lactate
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
16/17
16
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.
Metabolite accumulation - lactate
-
8/6/2019 Lecture Presentation - Fatigue - VisualBee
17/17
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
17
From: Matthews, CK & van Holde KE (1990) Biochemistry. Redwood City:Benjamin Cummings p.526.