Post on 17-Dec-2015
Muscular fatigueMuscular fatigue
Muscular fatigueMuscular fatigue
Inability to maintain a given Inability to maintain a given
exercise intensity or force exercise intensity or force
outputoutput
Muscular fatigueMuscular fatigue
No one cause of fatigueNo one cause of fatigue
Multifocal phenomenonMultifocal phenomenon
Central and peripheral componentsCentral and peripheral components
Metabolic fatigue results from:Metabolic fatigue results from:
Depletion of key metabolites which Depletion of key metabolites which
facilitate contractionfacilitate contraction
Accumulation of metabolites which impair Accumulation of metabolites which impair
contractioncontraction
Metabolite depletion - Metabolite depletion - phosphagensphosphagens
Phosphagen depletion Phosphagen depletion
associated with fatigue associated with fatigue
during short duration during short duration
high-intensity exercisehigh-intensity exercise
Copyright 1997 Associated Press. All rights reserved.
Metabolite depletion - Metabolite depletion - phosphagensphosphagens
Immediate source of ATP rephosphorylation is Immediate source of ATP rephosphorylation is
phosphocreatine (PCr)phosphocreatine (PCr)
Creatine kinase functions so rapidly that muscular ATP Creatine kinase functions so rapidly that muscular ATP
affected little until PCr significantly depletedaffected little until PCr significantly depleted
ATP and PCr concentrations in resting muscle are lowATP and PCr concentrations in resting muscle are low
Utilisation must be matched by restoration otherwise Utilisation must be matched by restoration otherwise
stores rapidly deplete and fatigue occursstores rapidly deplete and fatigue occurs
Metabolite depletion - Metabolite depletion - phosphagensphosphagens
During exercise at set work During exercise at set work
load PCr decreases in two load PCr decreases in two
phasesphases Rapid initial declineRapid initial decline
Slower secondary declineSlower secondary decline
Slower due to glycolysis and KC Slower due to glycolysis and KC
increasing ATP production which increasing ATP production which
rephosphorylates PCrrephosphorylates PCr
Both initial decline and extent of Both initial decline and extent of
final decrease related to relative final decrease related to relative
exercise intensityexercise intensity
Adapted from: Brooks GA & Fahey TD. (1985) Exercise Physiology: Human Bioenergetics and its Applications. New York:
MacMillan. p705
Metabolite depletion - Metabolite depletion - phosphagensphosphagens
ATP declines initially during ATP declines initially during
onset of exercise, but well onset of exercise, but well
maintained during steady-maintained during steady-
state exercisestate exercise
ATP hydrolysis buffered by ATP hydrolysis buffered by
PCrPCrAdapted from: Brooks GA & Fahey TD. (1985) Exercise
Physiology: Human Bioenergetics and its Applications. New York: MacMillan. p705
Metabolite depletion - Metabolite depletion - phosphagensphosphagens
Fatigue coincides with PCr Fatigue coincides with PCr
depletiondepletion
Once PCr stores depleted ATP Once PCr stores depleted ATP
concentration fallsconcentration falls
Associated with fatigue during Associated with fatigue during
short duration, high intensity short duration, high intensity
exerciseexercise
Adapted from: Sahlin K. (1986) Metabolic changes limiting muscle performance. In: B Saltin (Ed) Biochemistry of Exercise
VI. Champaign: Human Kinetics. p334
Metabolite depletion - Metabolite depletion - phosphagensphosphagens
Formation of ATP from PCr Formation of ATP from PCr
hydrolysis consumes Hhydrolysis consumes H++
Important buffering effect Important buffering effect
during high intensity exerciseduring high intensity exercise
ADP + PCr + H+ ATP + Cr
Metabolite depletion - glycogenMetabolite depletion - glycogen
Glycogen depletion Glycogen depletion
associated with fatigue associated with fatigue
during prolonged during prolonged
submaximal exercisesubmaximal exercise
Metabolite depletion - glycogenMetabolite depletion - glycogen
Slow-twitch fibres become glycogen depleted first, followed Slow-twitch fibres become glycogen depleted first, followed
by fast-twitchby fast-twitch
Same pattern occurs during high and low intensity exercise due Same pattern occurs during high and low intensity exercise due
to Henneman’s size principleto Henneman’s size principle
Rate of depletion accelerated during high intensity exerciseRate of depletion accelerated during high intensity exercise
Possible to fatigue due to glycogen depletion from specific Possible to fatigue due to glycogen depletion from specific
muscle fibres when glycogen remains in other fibresmuscle fibres when glycogen remains in other fibres
Lactate shuttle offsets this effectLactate shuttle offsets this effect
Metabolite depletion - glycogenMetabolite depletion - glycogen
Liver releases glucose to offset reduction in Liver releases glucose to offset reduction in
muscle glycogenmuscle glycogen
When liver and muscle glycogen depleted acetyl When liver and muscle glycogen depleted acetyl
CoA formed fromCoA formed from
-oxidation-oxidation
glucose derived from gluconeogenesisglucose derived from gluconeogenesis
This slows formation of acetyl CoA (and ATP) so fatigue This slows formation of acetyl CoA (and ATP) so fatigue
occursoccurs
Metabolite accumulation - Metabolite accumulation - lactatelactate
During moderate-high intensity During moderate-high intensity
exercise lactic acid accumulates exercise lactic acid accumulates
within the active muscles and bloodwithin the active muscles and blood
Lactic acid 99.5% dissociated at Lactic acid 99.5% dissociated at
physiological pHphysiological pH
Lactic acid accumulation associated Lactic acid accumulation associated
with fatiguewith fatigue
Lactate ion involved in fatigueLactate ion involved in fatigue
– Mechanism not knownMechanism not known
HH++ ion involved in fatigue ion involved in fatigue
– Number of possible mechanismsNumber of possible mechanisms
Metabolite accumulation - Metabolite accumulation - lactatelactate
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 ion involved in CK reaction and will displace
reaction to favour PCr breakdownreaction to favour PCr breakdown
– ADP + PCr + H+ ATP + Cr
Inhibition of PFK (widely accepted)Inhibition of PFK (widely accepted)
HH++ shown to inhibit PFK in vitro shown to inhibit PFK in vitro
– In vivo, increases in AMP, ADP and F 6-P overcome this In vivo, increases in AMP, ADP and F 6-P overcome this
inhibition so that glycolytic rate is retainedinhibition so that glycolytic rate is retained
Metabolite accumulation - Metabolite accumulation - lactatelactate
HH++ ion may contribute to fatigue via: ion may contribute to fatigue via:
Displacement of CaDisplacement of Ca2+2+ from binding with from binding with
troponin Ctroponin C
Failure to form cross-bridges and develop Failure to form cross-bridges and develop
tensiontension
Stimulation of pain receptors within muscleStimulation of pain receptors within muscle
Negative feedback mechanism (protective Negative feedback mechanism (protective
effect)?effect)?
Inhibition of triacylglycerol lipase activityInhibition of triacylglycerol lipase activity
Reduced lipolysis will increase reliance on Reduced lipolysis will increase reliance on
CHO as fuel, leading to earlier glycogen CHO as fuel, leading to earlier glycogen
depletiondepletion
Adapted from: Tortora GJ & Grabowski SR. (2000) Principles of Anatomy and Physiology (9th Ed). New
York: Wiley. p279
Metabolite accumulation - Metabolite accumulation - lactatelactate
Recent evidence suggests that Recent evidence suggests that
intracellular acidosis may actually intracellular acidosis may actually
protect against fatigue by protect against fatigue by
enhancing the ability of the T-tubule enhancing the ability of the T-tubule
system to carry action potentials to system to carry action potentials to
the sarcoplasmic reticulumthe sarcoplasmic reticulum
K+ accumulation in T-tubules during K+ accumulation in T-tubules during
muscle contraction reduces muscle contraction reduces
excitability of T-tubules (due to excitability of T-tubules (due to
inactivation of some voltage gated inactivation of some voltage gated
channels)channels)
Reduces ability to carry electrical Reduces ability to carry electrical
signals to sarcoplasmic reticulumsignals to sarcoplasmic reticulum
– Reduced release of calcium from SR Reduced release of calcium from SR
results in fewer cross-bridges being results in fewer cross-bridges being
formed and loss of forceformed and loss of force
Adapted from: Pedersen et al. Intracellular acidosis enhances the excitability of working muscle. Science 305:1144-1147, 2004.
Metabolite accumulation - Metabolite accumulation - calciumcalcium
CaCa2+2+ released from released from
sarcoplasmic reticulum may sarcoplasmic reticulum may
enter mitochondriaenter mitochondria
Increased CaIncreased Ca2+2+ in mitochondrial in mitochondrial
matrix would reduce electrical matrix would reduce electrical
gradient across inner membranegradient across inner membrane
Would reduce HWould reduce H++ flow through flow through
ATP synthaseATP synthase
– Reduced ATP productionReduced ATP production From: Matthews, CK & van Holde KE (1990) Biochemistry. Redwood City:Benjamin Cummings p.526.