BPK 310 - Lecture 8

Transient negative effects of acute exercise

Fatigue

Accumulation of metabolic wastes

Dehydration, fluid balance disruptions

Electrolyte disturbances

Muscle damage and delyaed onset muscle soreness

Oxidative stress

Inflammation

Fatigue, Description, Risk, Mitigation Strategy

Decrease in force or power production in response to contractile activitiy, can lead to task failure, the inability to sustain a force or pwoer adequate to accomplish a physical task. can be peripheral or central

risk of peripheral: certain - more important for high-intensity exercise, this is at muscle

risk of central: high - more important for prolonged moderate - or heavy - intensity exercise, at the brain

Apply progressive overload, consume CHO during exercise, pacing

Accumulation of metabolic wastes, Description, Risk, Mitigation Strategy

Amino acid ocidation and purine deamination producce nitrogenous wastes that can cause central fatigue and are highly neurotoxic (eg. NH4+, urea)

Certain, expecially in prolonged exercise

No mitigation strategy, it just will happen

Dehydration, Description, Risk, Mitigation Strategy

Reduced plasma volume, skin blood flow, thermoregulation

Certain

Consume liquids during exercise, especially in the heat

Electrolyte disturbances, Description, Risk, Mitigation Strategy

K levels rise in blood and intersitium - can interfere with muscle contractions

typically important only for prolonge exercise

Proper hydration and nutrition

Muscle damage (DOMS), Oxidative stress, inflammation, Description, Risk, Mitigation Strategy

Will be described later

High with unaccustomed eccentric contractions (DOMS)

risk is unknown for oxidative stress

High with sevre prolonged and intense exercise (inflammation)

Apply progressive overload, avoid trying to block these responses with drugs

Fatigue can depend on

The muscle fibers recruited

Slow oxidative fibers (type I) are fatigue resistant and will not show a substantial force decrease unless there is no fuel

Fast glycolytic fibers show marked fatigue

How is fatigue caused

Can be caused by limitations in either energy demand, energy supply, or both

Failure to consume energy sufficiently fast for the task (eg. inhibition of demand processes by metabolites)

Failure to supply energy sufficiently fast to meet demand (eg. depletion of substrate)

Hard to find cause of fatigue, but many correlates

Likely fatigue mechanisms at different intensities (at moderate, heavy, severe, extreme)

Moderate: hyperthermia (in the heat), reduced central drive/motivation (central fatigue), muscle damage

Heavy: glyocgen depletion, hyperthemia

Severe: depletion of finite energy store, accumu.ation of fatiguing metabolites, ATP supply issue

Extreme: as for severe, but also contraction coupling failure

Boundaries of exercise domains

Moderate: Upper - LT

Heavy: Lower - LT, Upper - CP

Severe: Lower - CP, Upper - highest power that elicits VO2max before fatigue

Extreme: Lower - highest power that elicits VO2max before fatigue

Central vs peripheral fatigue

Central: progressive reduction in voluntary activation of muscle during exercise

Peripheral: disruption of force-producing ability due to factors at or distal to the neuromuscular junction

Fatigue can occur at all sites along the force production pathway (eg. from motor cortex, to neuromuscular junction, to sarcomere)

Mechanism of peripheral fatigue, substrate depletion of phosphagens

PCr drops as function of intensity, its depletion is a causal agent of fatigue, and happens very rapidly

ATPs overall concentration is well maintained except for exercise at highest intensities (eg. super max sprints as it drives down stores and ability to produce)

It is possible that ATP concentration varies locallyand that it is depleted at sites of use

Free energy of ATP hydrolysis decreases; i.e less energy availble to do work per hydrolyzed ATP due to a build up of products

Mechanism of peripheral fatigue, substrate depletion of glycogen

Glycogen depletion depends on duration and intensity

At 50%VO2max, theoretically the stores will not deplete, especially as you commonly consume CHO while doing it

At 75% VO2 max, the stores will deplete (for someone with VO2max = 60) at around 180 mins

At 95% VO2max, the stroes will deplete (for someone with VO2max = 60) at around 60 mins

At 100% VO2max, it would theoretically take 30 mins to deplte glycogen stores but it is not possible to go that long at that intensity due to other issues

**Duration until depletion also depends on persons regular consumption of CHO

Mechanism of peripheral fatigue, substrate depletion, impaired availbility of energy from carbs and lipids

Blood glucose has three sources, liver glucogen, dietary intake, gluconeogenesis from liver (from lactate)

Prolonged exercise near or above LT: liver glycogen depletes, rate of gluconeogensis decreased dut to reduced blood flow to lover → blood glucose levels decrease

Glucose available to brain decreases - exercise feels more difficult

Lipids, cataplerosis (loss of TCA intermediates) decreases fatty acid oxidation, inhibition of fat oxidation enzymes

Mechanism of peripheral fatigue, reduced O2 availability

Adequate O2 is essential to sustain muscular work

Factors decuing O2 transport: decreased blood volume = decreased cardiac output, and blood flow redistribution away from working muscle as the brain still requires a certain amount of blood

This is definitely an issue at high altitude, or during ischemic event, or when hypoxic

Mechanism of peripheral fatigue, metabolite accumulation

Inorganic phosphate, inhibits PFK, and interferes with Ca binding to troponin

H (decreased pH):

causes protons dissociate form several acidic moleucles such as the products of ATP hydrolysis and severeal glycolytic intermediates being weak acids

consequences: can interfer with Xbridge cycling, inhibits PFK and hormone-sensitive lipases, displaces Ca from troponin, displaces O2 from Hb (good for at muscles, not at lungs), low pH affects brain and causes pain, nausea, and disoreintation

Mechanism of peripheral fatigue, impaired Ca handling

Interference with Ca effects

Sensitivity of contractile apparatus reduced (H, Pi)

Reduced Ca release from SR: loss from SR/slower relaxation due to reduced SR uptake (less recovery = less force production in next cycle)

The muscle metabolic environment is ______ at task failure at different durations of severe-intensity exercise

Would we see the same thing in the heavy-intensity domain?

Similar

No we wouldn’t, as different mechanisms of fatigue

What is central fatigue and what is the mechanism

The decrease in torque/power secondary to a decrease in voluntary muscle activitiation

Feedback from muscle group III and IV afferents reduces central motor drive, they may exert inhibitroy feedback effects

What is psychological fatigue

Succumb to exertion-related discomforts

Pain, nausea, weakness, dyspnea, side stitch, cramp, hunger, sleepiness, etc.

Following exercise, we need recovery which consists of:

Rplenish substrates: phsophagens, glycogen, lipids

Dispose of emtabolites that impair force production

Restore fluid and electrolyte balance

Dissipate heat

Repair damage

Manage inflammation

Precise recovery kinetics will depend on many factors:

Degree of substrate consumption/metabolite accumulation (volume and intensity of exercise)

Recovery context: availability of substrates, environmental conditions

Fitness of individual

Timescale

Time allowed for or taken by a process for a sequence of events

Express in the different units of time: seconds, mins, hours, etc.

Phosphagen recovery

Requires O2 supply

With intact circulation 90% of PCr can recover in 4 minutes, and 100% at ~5 mins

Time course of glycogen replensihment during recovery

Can take 24hrs (~1-2 days) to recover

But depends on CHO availability, complete resynthesis requires a high dietary intake of carbs during at least a two-day period.

Glycogen will accumualte more rapidly after intense intermittent exercise, and following intermittent exercise a significant amount of glycogen is resynthesized during the first 2 hours of recovery even in absence of food intake. Still, complete resynthesis requires 24 hours

Why might differences exist between post-continuous and intermittent exercise in glycogen recovery

Amount deplete: continous > intermittent

Availability of precursors: higher with intermittent (higher glucose release during intense exercise)

Fibre type differences: type II fibers resynthesize glycogen faster than type I and they are recruited more during intense intermittent exercise

Since glycogen progressively depletes in response to successive exercise bouts, what what happens as a result of consecutive training bouts

It results in overall lowered glycogen

Eg. muscle glycogen is progressively depleted during a three-day pariod when 16km are run each day

Liver glycogen depletes with?

Exercise and starvation and can “supercompensate” in response to high-CHO diet

Maximizing post-exercise glycogen resynthesis

Type and amount: carbohydrate (1-1.5 g/kg/hr) should be consumed, ingestion of carb:protein mixture may enhance glycogen resynthesis but only if less-tahn-optimal CHO is consumed (<0.8/g/kg/hr)

Timing:

• Biphasic - initial rapid resynthesis 30-60 min post-exercise if exogenous CHO is available (possible due to insulin-independent GLUT4 translocation).

• Slow resynthesis (80% slower) via insulin-mediated pathways

Glycogen resynthesis rates highest when feeding occurs immediately after exercise. Nevertheless, glycogen levels will recover no matter the time of feeding, just more slowly

If rapid recovery is sought = feed as soon as possible after exercise

Lactate recovery kinetics and fates

Lactate is important for replensighing glycogen and for supplying other energy processes

Timescale = minutes to hours

Lactate is removed from blood and muscles during recovery from exhausting exercise, in general 25 mins of rest-recovery are required to remove half of accumulated lactate

It will be metabolically converted to glucose, protein, glycogen, CO2, and H2O (oxidized).

Oxidation occurs primarily in type I skeletal muscle fibers

Lactate recovery kinetics: passive vs. active

Active recovery (i.e light exercise during recovery) causes faster lactate removal, primarily due to increased oxidation by working type I muscle fibers.

For untrained subjects recovery exercise that produces fastest/optimal rate of lactate removal in one in which VO2 is between 30-45% max

Blood pH, bicarbonate, lactate levels following time-to-exhaustion tests with 35 min recovery between

blood pH: recovers almost to baseline within 35 min recovery

HCO3: recovers about ½ within 35 min recovery

blood lactate: is still heightened within 35 min recovery

Recovery of lipids, amino acids, and electrolytes

Depends on type (eg. continous, intermittent), intensity and duration of exercise

Lipids

• arterial FFA increase post-exercise due to blood flow redistribution

• blood FFA and glycerol levels are elevated for hours )12+) post-exercise (energy source for recovery)

Amino acids

• liver gluconeogenese enhanced post-exercise

Electrolytes

• muscle and arterial; recoveries typically follow first-order kinetics

• pH - minutes to hours

• K - recovers in minutes (5-30)

• Pi - recovery in minutes (5-10)

Excess post-exercise O2 consumption

“recovery oxygen”

Area under the VO2 curve above resting VO2

timescale = minutes

Provides oxygen for oxidative phosphorylation, which supplies energy for recovery processes

Kinetics are biphasic

Kinetic components of excess post-exercise O2 consumption

Fast component: ~0.5-4 L O2

• resaturate myoglobin with O2

• replensih phosphagens

• O2 cost od increased Ve and cardiac work

Slow component: ~5-14 L O2

• elevated body temp

• catecholamine-stimualted metabolism

• O2 cost of increased Ve and cardiac work

• increased Na-K-ATPase activity

Some negative effects of exercise are considered “damage” these are:

Oxidative modifications of proteins (oxidative stress)

Muscle damage and soreness

Inflammation

Muscle contration increases rate of free radical production, this does what?

They exert positive and negative effects on the cell

Primary reactive oxygen and nitrogen species (eg superoxide, O2-, H2O2) produced inv arious sites inside and outside muscle cells, happens by accident in ETC or any time we use O2

Positive effects:

• help maintain force production (Ca handling), glucose uptake, insuling signalling

• Promote exercise training adaptations through transcription control

• Promotes muscle antioxidant defence

Negative effects:

• oxidative stress: excessive or poorly lcocalized free radical oxidize lipids, DNA and proteins

Unfamiliar eccentric exercise causes:

Muscle damage and delayed-onset muscle soreness (DOMS - feel 24-48 hrs and then gets worse over a couple days)

Common training techniques and exercise modalities involve eccentric contractions

Eg. walking/running downhill, climbing or stepping down stairs, lower phase of a bicep curl, landing phase of a jumping exercise

Consequences of muscle damage

Prolonged (days to weeks) loss of function

Reduced strength

reduced mobility

pain

swelling

Second bout effect: same activity again will cause significantly less pain/DOMS

Biochemical and histological symptoms of muscle damage/DOMS

Elevated muscle enzymes in blood: creatine kinase, lactate dehydrogenase, etc

Ultrastructural damage

Immune cell infiltration

Degradation and regeneration of muscle fibers

Kinetics of muscle function recovery in response to damaging exercise

Maximal voluntary contraction force normally recovers within ~3 weeks

Muscle enzymes _____ in blood in response to damaging exercise. Which ones?

Accumulates

Creatine kinase and lactate dehydrogenase

Role of muscle damage and repair in the training response is controversial

Muscle damage is limited beyond the resposne to the original eccentric exercise (eg. repeated bout effect, it reacts to damage by producing an adaptive response that endows resistance to subswwequent exercise-induced damage stimuli)

Training is often viewed as a “cycle of breakdown and repair” and that fatigue/damage are necessary to training: NOT nedcessarily true, adaptations to training result from signalling mechanisms that are stimulated from exercise, magnitudes of stimuli are proportion to exercise duration/intensity, so are negative effects of exercise, mostly correlative, perhaps a partly causal relationship between damage processes and training adaptation

Autophagy and mitophagy, cellular process that involves intraceullar degradation of organelles and other components via the lysosomal pathway, exercise-training adaptations require autophagy

Mitophagy pathway

Damaged mitochondria are tagged for autphagy

Mitochondria are enveloped in a membrane formning a complex called an autophagome

A lysosome attached to the autophagosome forming an autolysosome

Enzyme are released and difest the mitochondria

Inflammation caused by exercise

Exercise elicits the acute phase response, the coordinated systemic response to infection or aseptic damage

Cytokines and acute phase proteins have an increase in blood concentration in the hours to days following stimulus

Acute phase response in trained athletes following prolonged strenuous exercise

Elevated IL-6 (interleukin-6) precedes elevated CRP (c-reactive protein)

**both are cytokines that are released in response to acute inflammation

Post-exercise cold water immersion

Attenuates acute anabolic signalling and long-term adaptations in muscle to strength training (blunts training process)

Antioxidants

Research has shown they prevent health-promoting effects of physical exercise in humans

Summary of “damage” due to exercise

Not exclusively bad, they reflext natural physiolgoical processes that have psotiive effects deal with aseptic damage. While exercise may cause inflammation, exercise training reduces chronic low-grade inflatmmation associated with disease

Taking antioxidant or anti-inflammatories may suppress training adaptations

Muscle damage/DOMS result primarily from unaccustomed eccentric exercises

Damage biomarkers are used to monitor athletes during training

After a strenuous competition, feverish due to acute phase response, blood profile resembes that from myocardial infarction