1. Fatigue
Brooks Ch 33

2. Outline Definitions Exhaustion (depletion) Hypothesis
Central Fatigue
Peripheral Fatigue
Exhaustion (depletion) Hypothesis
Phosphagens
Glycogen / glucose
Accumulation Hypothesis pH
Phosphate
Calcium
Potassium (Foss p 65)
Oxygen
Future of Fatigue

3. Fatigue During Exercise
Fatigue - inability to maintain a given exercise intensity or power output
Reversible with rest (recovery)
rarely completely fatigued - can maintain lower intensity output
Studied with EMG and observation of contractile function with electrical (nerve) or magnetic stimulation (cortex)
Observe reduction in force and velocity and a prolonged relaxation time after fatigue
The effect of exercise at an absolute or relative exercise intensity will be more severe on an untrained individual

5. Advanced Neuromuscular Exercise Physiology - Human Kinetics 2011

7. Fatigue During Exercise
Causes of muscle fatigue have been classified into central and peripheral
Central - includes CNS, motivation and psychological factors
restoration of force with external stimulation of muscle -indicates central fatigue
NH3, hypoglycemia, reticular formation
Peripheral - PNS to muscle - EC coupling, energy supply and force generation

8. Exercise Metabolism - Human Kinetics - 2006

9. Exercise Metabolism - Human Kinetics - 2006

11. Identifying site of Fatigue
fatigue can be identified specifically - eg. Glycogen, Ca++ depletion
Compartmentalization within the cell increases the difficult of determining the source of fatigue
eg. ATP may be depleted at the myosin head, but adequate elsewhere in the cell - is this detectable?
Often the origin of fatigue is diffuse
eg dehydration
several factors then contribute to a disturbance of homeostasis
Often easier to identify correlations to fatigue, rather than causal contributions to fatigue

12. Environment and Fatigue
Heat and humidity - can affect endurance performance
inc sweat, heat gain, dehydration, changes in electrolytes results in
redistribution of Cardiac Output
Uncoupling of mitochondria - less ATP with same VO2
changes in psychological perception of exercise
Fatigue is cumulative over time
dehydration yesterday can influence performance today
Glycogen depletion cumulative as well
Reduced circulation to muscle may result in glycogen depletion
Reducing endurance capacity

13. Central Fatigue
possible to have fatigue w/out the muscles itself being fatigued
eg pain may affect drive to continue
Compare force output during fatigue with force output during maximal external stimulus (eg electrical impulse on motor nerve)
An ability of this external stimulation to restore force would indicate central fatigue
Psychological Fatigue
understanding is minimal
With training - athletes can learn to minimize influence of sensory inputs
Able to approach performance limits

14. Central Fatigue Central fatigue - Stechnov Phenomenon
Fig faster recovery of strength with distraction or “active pauses” during recovery from exhaustion

15. Peripheral Fatigue
Fig ulnar stimulation is constant - force development decrease over time - indicating peripheral fatigue

16. Peripheral Fatigue
Fig large increase in EMG signal - no increase in force - also indicates peripheral fatigue (see slide 5)

17. Peripheral Fatigue Two hypothesis for peripheral fatigue
a) Exhaustion - depletion of energy substrates - eg ATP, CP, glycogen
Phosphagens are present in low quantities
Must match use with restoration from other metabolic pathways - or fatigue
b) Accumulation of metabolic byproducts - eg H+, Ca++, Pi
Likely a combination of factors with contributions influenced by the specific conditions of the activity

18. Exhaustion Hypothesis
Depletion of metabolites
Phosphagens
Fig 33-2a - CP levels decline in two phases - drop rapidly, then slowly
Rate of ATP synthesis by CK decreases along with decrease in CP content - rate is fastest at rest

19. Exhaustion Hypothesis
both severity of first drop and extent of final drop related to work intensity
fig 33-3

20. Exhaustion Hypothesis
Fig 33-2b - ATP well maintained
compartmentalization?
Down regulation / protection theory?
ms cell shuts off contraction - with ATP depletion in favor of maintaining ion concentration gradients and cell viability

21. Depletion (continued)
Glycogen
depletion associated with fatigue
moderate activity - uniform depletion from different fiber types
Also activity specific fiber depletion
Carbohydrate loading can improve performance
Caffeine (inc FFA mobilization) can also offset fatigue
Blood Glucose
During short intense exercise bouts - blood glucose rises
With prolonged activity- blood glucose may fall
Fatigue at blood glucose below 3.5 mM
Anapleurotic substrates
Krebs cycle intermediates - decline results in reduced capacity of Krebs

24. Accumulation Hypothesis
H+ (acidity)
Lactic acid accumulates during short term high intensity exercise
As production exceeds removal
exported into blood from muscle
As it is a strong acid -blood pH decreases
H+ in blood - affects CNS
pain, nausea, discomfort, disorientation
inhibits O2 / Hb combination in lung
reduces HS lipase - dec FFA oxidation
**still unsure if this induces fatigue**

25. Accumulation Hypothesis
muscle acidosis
all glycolytic intermediates are weak acids
ATP breakdown also produces H+
may inhibit PFK - slowing glycolysis
may interfere with calcium binding TnC
may stimulate pain receptors

26. Phosphate( Pi) and Diprotenated phosphate (H2PO4)
Accumulation
Phosphate( Pi) and Diprotenated phosphate (H2PO4)
phosphagen depletion (CP) - results in Pi accumulation
behaves like proton
inhibiting PFK
interfering with X-bridge attachment, detachment and force production

27. Accumulation Fig 33-4 H2PO42- acid and Pi
indicative of non steady state - fatigue

28. Accumulation Calcium Ion Accumulation
mitochondrial coupling efficiency
some Ca++ stimulates Krebs cycle
accumulation - requires energy to remove the calcium
Creates oxidative phosphorylation uncoupling in test tube
exacerbated by reduced Ca++ sequestering by SR with fatigue

29. Calcium (cont)
Fig changes in Ca++ flux and signaling in fatigued muscle
Po refers to max isometric force

30. Calcium (cont) symptoms of fatigue (fig 33-5) 1. dec free calcium
decreased force generation - with single or tetanic stimulation
related to SR Ca++ release, and/or pH affects on opening of SR channels
1. dec free calcium
May be EC coupling at T tubules, sarcolemma, or SR channels
Accumulation in mito, dec SR uptake
Lactate anion interference with ryanodine receptor
Pi precipitation with free calcium
2. Responsiveness - down shift
H+ interference with Ca++ binding
3. Sensitivity - small L-R shift
given free Ca++ - less force
less impact than dec release or responsiveness

31. Potassium (K+)
Foss p 65
K+ is released from contracting muscle resulting in
reducing cytosolic and an increasing plasma K+ content
Release high enough to block nerve transmission in T tubules
Concomitant increase in Na+ intracellulary disrupts normal sarcolemmal membrane potential and excitability
High Na+/K+ pump activity improves performance
Rapid recovery of K minutes
Complete in ~30 minutes
During exercise inactive tissues take up K+

32. O2 depletion and Mitochondria
O2 depletion and Mito density
dec in ms O2 or circ O2 can lead to fatigue eg - altitude, circulation impairments
low O2 often indicated by lactate accumulation, CP depletion or both
exercise depends on integration of many functions - any upset -- fatigue
Doubling of oxidative capacity with training
increases use of FFA -sparing glycogen
Minimizes impact of the damaging effects of free radicals

33. Advanced Neuromuscular Exercise Physiology - Human Kinetics 2011

34. Heart Fatigue Heart as site of Fatigue
no direct evidence that heart is site of fatigue
Arterial PO2 is maintained during exercise, heart gets Q priority
heart can utilize lactate or FFA
ECG - no signs of ischemia at maximal effort or fatigue
if there are signs- heart disease is indicated
With severe dehydration... Cardiac arrhythmia is possible

35. Future of Fatigue
Technology is making available new devices - further investigation of fatigue
NMR
possible to determine [ ] of Phosphagens, protons, water, fat, metabolites
without breaking the skin
Fig 33-11
a at rest - before fatigue
b after fatigue
area under curve represents [ ] of metabolites (ATP, CP, Pi)
Clear indication of declines and accumulations at fatigue
Table 33-1 comparison of values
NMR vs muscle biopsy

37. Fig. 1. Estimation of critical power (CP) in a representative subject
Critical Power - highest constant work rate
that can be maintained without fatigue
Jones, A. M. et al. Am J Physiol Regul Integr Comp Physiol 294: R585-R ;
doi: /ajpregu
Copyright ©2008 American Physiological Society

38. Exercise Metabolism - Human Kinetics - 2006