Future Questions: jackson.fyfe@deakin.edu.au

Topic 0: Physiology Overview

The study of normal function in a living system: extends to plants and animals.

It includes many levels of function and integration including, gross anatomy, movement, organs, tissues, cells, chemicals, molecules and their practical application of how our environment influences these systems.

What is Exercise Physiology:

The effect exercise has on physiological systems. Includes the study of environments, elite performance, ageing, rehabilitation

Hippocrates (460 BC)

“If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health.”

---

Topic 1: Muscle

Lectures 1 and 2 – Muscle Contraction (Parts 1 and 2)

Ordered Segments of Skeletal Muscle

MFFMS

MUSCLE > FASICLE > FIBRE > MYOFIBRIL > SARCOMERE

Connective Tissue Layers

Fascia

Superficial (under skin)

Encapsulates all body tissues (e.g. muscle and bone)

Epimysium

Surrounds individual whole muscles (thick)

e.g. in quadriceps, each muscle in the group has its own epimysium

Perimysium

Surrounds each fascicle (10-100 fibres)

Contains blood vessels, motor axons and muscle spindles (intrafusal muscle fibres)

Endomysium

Surrounds 1-2 muscle fibres

Provides basement membrane and a framework for regeneration

Generated by fibroblasts resident between fibres

Sarcolemma: cell/fibre membrane (lipid bilayer – i.e. not connective tissue)

Rippled (caveolae) at rest (allows stretch/lengthening without membrane damage)

More Extra Definitions:

Facical:

A collection of muscle fibres (muscle cells)

Sarcomere: The smallest force producing unit within a myofibril (AKA smallest functional unit within a muscle)

Myofibril = bundles of proteins that make up our muscle cell)

Muscle spindle: a reflex fibre provides info to the brain about the position and tension – level of force being generated by that fibre.

Muscle Fibres & the Sarcomere

Actin and myosin are proteins that generate force, they’re the ones that interact and cause cell shortening. Actin and myosin move across one another as force is produced. The proteins slide within the cell causing cell shortening (they can only operate in a shortening direction).

Step 1: Neuromuscular Transmission

Motor Unit: A somatic motoneuron and the muscle fibres it innervates

Individual muscle fibres are activated by a neuron > but the one neuron might activate many fibres > however that muscle fibre is only activated by a single neuron, not multiple neurons.

This is important because it means we can divide up a muscle into motor unit groups.

Neuromuscular junction:

The synapse between motoneuron and muscle fibre

Occurs at the “motor-end-plate” – only have 1 per muscle cell & several per motoneuron i.e. it innervates many muscle fibres

A neuron can activate many fibres but a muscle fibre is only activated by one neuron – so that muscle fibre is allocated to that motor unit 

Skeletal muscle motor end plate

Yellow: A single neuron what has multiple branches at the end of it touching onto multiple different muscle fibres making up that motor unit.

Step 1: Neuromuscular transmission

Action Potentials

Action potentials are nerve impulses.

Action potentials are propagated (moves along) changes in the transmembrane potential that, once initiated, affect an entire excitable membrane.

Yellow: Nerve / Orange: Motor end plate on the muscle cell 

1.An action potential (AP) arrives at the a-motoneuron terminal from the axon

2.That AP opens voltage-gated (sensitive to electrical activity) Ca2+ channels in the a-motoneuron terminal membrane

3.You get an influex of Ca2+ influx at a-motoneuron terminal

4.That Ca2+ activates migration of vesicles (purple circles) of the neurotransmitter ACh (acetylcholine) to the synapse > you get fusion of those vesicles of ACh with the cell membrane and…

5.ACh is released into synaptic cleft (white space) via exocytosis

6.ACh diffuses across the synaptic cleft

7.ACh binds to sarcolemmal nicotinic receptors in the motor end plate area

8.Those Nicotinic AChR’s receptors generate an End-Plate Potential (EPP) via Na+ (sodium) influx through the receptor into the cell

9.That EPP (end plate potential) migrates away from motor end plate – generating a current field – that field is big enough to get away from the motor end plate and…

10.EPP opens voltage-gated Na+ channels

11.Therefore an AP is generated in muscle cell

Step 1 complete: The muscle fibre has been stimulated electrically by a motoneuron and is now ACTIVE! (i.e. it is electrically excited and has it’s own action potential). IT’S BEEN STIMULATED TO CONTRACT BUT IT HASN’T CONTRACTED YET – IT’S ACTIVE AND IT COULD CONTRACT. THE NEXT STEP IS HOW DO WE TURN THIS ELECTRICAL SIGNAL INTO SOMETHING THAT IS PHYSICAL AND FORCE PRODUCING.

Summary: You get an AP in the terminal > it drives in influx of Ca2+ > the Ca2+ signals the neurotransmitter ACh to move to the surface > release it’s contents > ACh diffuses across the synaptic cleft (the white space) > activating the nicotinic receptor > causes a current that is big enough to drift outside the motor end plate and activate voltage sensitive Na+ channels in the regular muscle cell membrane > when they’re active you’ve got a AP in the muscle cell

We’re sending 30-40 APs down a neuron every second during a muscle contraction.

Essential skeletal muscle organelles

If we want to generate a coordinated contraction what we want to do distribute that AP across the length of the cell quickly and evenly. If that electrical signal is going to be the thing that causes a physical change in the cell to produce force, if it’s at the surface, what about all the contractile proteins that are packed below the surface in the middle of the fibre – how do we activate those?

The answer is explained partly through T-tubules whose function it is to rapidly and evenly distribute AP’s evenly across the length and depth of the fibre: The little green “perforations” on that diagram which are part of the sarcolemma. Then we have the sarcoplasmic reticulum that wraps around every individual myofibril which functions to store and release Ca.

Transverse tubules (T-tubules)

Is defined as a specialised conducting area of the sarcolemma

Invaginations of the sarcolemma (appear like perforating holes)

Penetrate deep into each muscle fibre

Approach each myofibril and, therefore, every sarcomere

Therefore, many per cell, and at regular intervals (2 tubules per sarcomere; evident at A-I junction)

T-Tubules function to rapidly and evenly distribute AP’s

Sarcoplasmic reticulum (Functions to store Ca2+)

Membrane network surrounding each myofibril

Two distinct regions:

1) Terminal cisternae (release Ca2+ into cytosol):

Sac like structures near the Z-line/I-band region

Forms a TRIAD with the T-tubules

2) Longitudinal tubules (uptake Ca2+ from cytosol):

Located around the A-band region

The skeletal muscle Triad

Step 2: Excitation-Contraction Coupling

The process of action potential transduction (changing from one form to another) to provide an intracellular signal (↑[Ca2+]i) causing a subsequent muscle cell contraction

i.e. coupling of Step 1 (electrical activation of the muscle fibre via an AP discussed above) to physical cell shortening

Most commonly focuses on the links between

T-tubule action potentials, and Sarcoplasmic reticulum which helps Ca2+ release.

Mechanism not entirely understood – for review read: Dulhunty AF. (2006). Excitation-Contraction coupling from the 1950s into the new millennium. CEPP 33, 763-772.

However, Much is understood about the function and interaction of key components:

T-tubule voltage sensor which detects electrical activity to sense an AP (Dihydropyridine receptor – DHP)

SR Ca2+ channel release mechanism (RYR receptor): primary function to store and release Ca2+

Just remember there’s a release channel for Ca2+ in the sarcoplasmic reticulum (SR) that’s going to help cause contraction.

This is what it looks like, the cell surface membrane (sarcolemma) is the blue line at the top > the T-Tubule runs down (cylinder) into the muscle fibre > it forms this triad with the 3 structures of the SR on either side and the tubule in the middle. In the T-Tubule we have our voltage sensors DHP receptors > lining the membrane of the SR are the RYR receptors (calcium release channels) > once we open those channels Ca2+ will come out of the SR where it’s stored and flood the cell with Ca2+.

Once the AP travels down the TT it hits the voltage sensor which is connected to the channel that stops the Ca2+ getting out. [Left] Then after the AP [Right] it opens the channel to have the effect to allow the Ca2+ that’s stored within the SR to flow out through the channel increasing the Ca2+ concentration in the cell.

The Myofilaments/Contractile Proteins

The mysosin heads generate force. The ATPase cite is an enzyme where energy (ATP) is used for a muscle contraction.

Another important cite is the binding cite for actin filaments. The myosin heads have the capacity to bind onto actin.

The actin filament comprises of monomers (black spots) – each of those monomers has these binding cites for myosin. Each black spot represents the capacity for myosin to attach to that monomer.

Actin and myosin aren’t always allowed to be in contact with each other otherwise we’d be having muscle contractions all the time. Muscle is naturally inhibited from contracting at rest via a filament called tropomyosin (pink) which lies over the binding cites for myosin (black spots – monomers)). So if there’s something obstructing the ability for actin and myosin to come together then we can’t cause a muscle contraction. Tropomyosin is a ‘regulatory proteins’.

Regulatory Proteins

Now we have a situation where we’ve activated our muscle with an AP > we released Ca2+ into the cell > the Ca2+ bound to the troponin > we got a physical change in our actin filament > now we’ve exposed the capacity for actin and myosin to come together and attach to each other to potentially generate force

Force production

Sliding Filament Theory^

More Info:

Bound State: Actin and myosin can only exist in a bound state when they’re binding cites are exposed and they can come together.

1. ATP is being generated regularly by all cells. In muscle when it’s relaxed you’re in a state that’s ready to contract, you’ve already used the energy and its’ stored within the myosin head. If gives you an immediate capacity to contract so you don’t have to wait to get energy, you’ve got it and now you’re waiting for the capacity to expend and release the energy.

3/4. Rigor (rigamortus) occurs because if you cannot produce any more ATP then we cannot get the detachment of actin and myosin filaments so muscles get very stiff when we die.

Which may contribute to increasing force output of an active muscle?

Step 3:The Cross-Bridge cycle

1. At rest myosin is energised

ATP has been cleaved to ADP, Pi (inorganic phosphate) and releases energy in the breakage of that bound

Energy is stored within the myosin protein

2.Ca2+ binds to troponin-C

3. The myosin binding site on actin becomes exposed

4. Myosin becomes bound to actin

5. Pi is released from myosin upon binding with actin

6. Myosin releases energy through the power stroke

7. Actin is dragged toward the interior of the sarcomere

This appearance provides the basis of the Sliding Filament Theory

8. Sarcomere length decreases, translating to whole muscle shortening = CONRACTION!

But we can also generate force without shortening, it’s just a way to explain the theory.

9. ADP is released from myosin during the power stroke

10. After power stroke myosin binds a new molecule of ATP

11. Actin and myosin detach

12. ATP hydrolysis occurs to re-energise myosin

13. Myosin head returns to the resting “cranked” position

14. If a high [Ca2+]i is maintained in the cell then the

CROSS-BRIDGE CYCLE CONTINUES!

Step 3 complete The muscle is now contracting functionally to perform WORK!

What causes that intracellular Ca2+ concentration to be maintained at a high level =  repeated stimulation from the brain to the muscle AKA action.

Lecture 2/7 44:00

Summary of How A Muscle Contracts

Signals travel from the brain down the spinal core to the muscles via long thing cells called motor neurons.

The motor neuron and muscle cell are separated by a tiny gap (synaptic cleft) and the exchange of particles across this gap enables this contraction.

On one side of the gap the motor neuron contains the neurotransmitter ACh, on the other side charged particles line the muscle cells membrane. K+ on the inside and Na+ on the outside.

It response from a signal from the brain the motor neuron releases ACh which triggers pores on the muscle cell membrane to open. As a result Na+ flow in and K+ flow out.

The change in charge creates an electrical signal called an action potential that spreads through the muscle cell stimulating the release of Ca+ that’s stored inside it. The flood of Ca2+ causes the muscle to contract but enabling proteins in the muscle fibres to lock together (actin and myosin) and ratchet towards each other pulling the muscle tight.

The energy used to help power the contraction comes from a molecule called ATP. ATP also helps pump the ions back across the membrane afterword reseting the balance of Na+ and K+.

This process repeats every time a muscle contracts.

How Does Fatigue Set In Then?

Eventually over the course of repeated contractions there may not be sufficient concentrations of K+, Na+ and Ca2+ immediately available near the muscle cell membrane to reset the system. So even if the brain sends a signal the muscle cell can’t generate the AP necessary to contract.

With the help of active K+ and Na+ pumps during rest muscle fatigue will subside as these ions replenish throughout the muscle.

When explaining the mechanisms behind peripheral fatigue it’s not just about how much ATP we use, lactate building and the pH of the muscle (remember: our muscles have a pretty good ability to buffer lactate and maintain pH) but rather it’s also important to emphasise depleted concentrations of K+, Ca2+ and Na+.

The stronger you are the longer it takes for muscle fatigue to set in each time because the stronger you are the fewer times this cycle of nerve signals from the brain to contraction in the muscle has to be repeated to lift a certain amount of weight. Fewer cycles means slower ion depletion so as your fitness and strength improves you can exercise for longer at the same intensity (increased work capacity).

#Post

http://muscle.ucsd.edu/musintro/jump.shtml

Getting an AP from that nerve terminal into the motor end plate > generating an AP in our muscle cell membrane that can travel down the t-tubule and activate our voltage sensor gates to cause a Ca2+ release > that Ca2+ can activate regulatory proteins to expose those binding cites > now we can get the cross bridge cycle to produce force > continue this cycle as long as we have APs delivered to the muscle and continuously Ca2+ to be released

Why do we need to continue to release Ca2+ when Ca2+ is already high in the first place? 

Because we are always overcoming relaxation. In fact the most rapid process within muscle is the capacity for muscle to relax. So given the choice muscle will usually always choose to relax.

---

Lecture 3, 4 & 5 Skeletal Muscle Fibre Types

Terminology

Muscle fibre types distinguish the classification of the type of myosin that exists within those fibres.

Type 1: S = Slow / SO = Slow Oxidative (Fatigue Resistant: Long Time)

Type IIa: FR = Fatigue Resistant / FOG = Fast Oxidative Glycolitic (<2 Minutes High Intensity: 200-800m)

Type IIx/IIb: FF = Fast Fatigable / Fast Glycolitic (1-30sec Maximal Intensity: 0-100m)

We always thought we had type IIb fibres in humans but we’ve recently discovered they only exist in rodents, what we actually have is a type of myosin that we call type IIx. But because that’s only recent you’ll still see older research that refers to type IIb but this is outdated.

Which fibres/what % of fibres can transition to become other fibres?

About 15 to 20% of muscles fibres have not differentiated into type I, type IIa or type IIb by birth (Baldwin, 1984, Colling-Saltin, 1980). There is some speculation that early motor activities might influence the final proportion of fibre type; however, this has yet to be determined in research (Haywood & Getchell, 2009).

Red versus White muscle

Muscle image from mouse that’s been genetically modified.

Transgenic (TG) has greater proportion of slow twitch compared to Wild Type (WT)

Note: ST and FT muscle fibres under a microscope don’t look any different, it’s just the fact there’s more capillaries in a whole muscle that distinguish whether it will be more red or white in colour

Typical Ultrastructural Appearance

ST fibre on the right has a lot of mitochondria (an oxidative/aerobic organelle that generates ATP) which corresponds to a ST fibre using much more O2 more efficiently, whereas the FT doesn’t have much mitochondria so the muscle will fatigue quicker under the presence of less mitochondria.

T1 fibres have less extensive t-tubule/SR system so force can be produced quicker and the AP can get through the cell quickly and enable contractile proteins to interact with the cross bridge cycle quickly.

Long sarcomeres infer a slower rate of contraction (have a long latency to produce force)

Soleus = ST Muscle / White Vastus = FT Muscle

A) Area of tubular system is larger in FT which means more rapid activation

B) More extensive SR in a FT fibre compared to ST

D) ST sarcomeres are larger and FT sarcomeres are smaller

The Problem

The Solution

Series A structure causes only half the sarcomeres to contribute to force production because they oppose each other and cancel one out.

Whereas when you arrange them in parallel there is no cancelling of force – they all can contribute = B would produce the greatest maximal force.

Normalise/Standardise Force

“CSA is the single biggest determinant of maximal muscle force.” [doesn’t take into account the CNS)

However, we often normalise force account for relative force per unit of CSA.

Force production from different fibre types

Muscle fibre size (i.e. cross-sectional area)

Type 2 fibres can form more cross bridges than Type 1 fibres.

Reading

An example that muscle fibre size and force production may not always fit the classic textbook assumptions and that myosin type  that dictates the type of fibres we have.

‘The Pump’: Caused by fluid (water) getting into a muscle cell will contribute to changing it’s size.

Types of Muscle Contractions

Isotonic (dynamic)

Muscle length changes during contraction

Concentric contraction (agonist muscle)

Muscle shortens and joint angle decreases e.g. the biceps muscle during the lifting phase of a biceps curl

Eccentric contraction (antagonist muscle)

Muscle lengthens and joint angle increases e.g. the triceps muscle during the lifting phase of a biceps curl e.g. the quadriceps “bracing’ action during downhill walking/running

Isometric (static)

Muscle length remains constant during contraction e.g. pushing against a wall or immovable object. Often research is done on iso contractions because it’s not complicated by the influence of fibre type

When we stimulate with a higher frequency we get more force output from the muscle.

When we get to a high enough frequency we get to a tetanic contraction which is our maximum force we can get out of a muscle during high frequency stimulation.

Muscle fibre twitch contractile properties

Muscle fibre tetanic contractile properties

Different frequency stimulation produce different force outputs depending on fibre twitch type.

Slow twitch fibre types have lower overall tetanic contractions at lower stimulation frequencies

But we rarely use this method of change in stimulation frequency (about 10% of the time) to change force output. 90% of the time we change the number of motor units we recruit.

2 Ways To Vary Force Output

1) Change stimulation frequency

2) Recruiting a different amount of muscle tissue

Muscle fibre types
(contractile properties partly explained)

P0 = Maximum Force

ST fibres and slow contractions don’t have enough time to generate force.

The longer we can make Ca2+ stay in the cell by stimulating it to be released on a regular basis at a higher frequency, then we can generate more force. It’s not that there’s more Ca2+, it’s just that were not allowing that Ca2+ to be removed from the cytoplasm before we stimulate it again. So all high frequency stimulation is doing is generating a large concentration of Ca2+ around the contractile proteins and were maintaining that at a high level by continually releasing it and overcoming the speed at which Ca2+ can be removed from the cell.

FT fibres have faster relaxation times than ST so because FT relaxes more quickly and removes the Ca2+ more quickly we need a greater frequency of stimulation to get that Ca2+ up again. The faster it’s taken away the more we need to stimulate that muscle. FT requires a greater stimulation frequency to be able to produce those high contraction forces.

Again, we only do this 10% of the time. Why we’re going into so much depth for something that’s done 10% of the time I don’t know.

Force, Velocity of shortening, and Power

Even though force is constant, greater distance is covered with the FT fibre meaning a greater power output over the same amount of time is produced via FT.

Muscle fibre contractile properties (fatigue resistance)

The vertical shaded lines to show the number of stimuli delivered to the muscle fibre AKA potential force output.

Muscle fibre types
(biochemistry/metabolism)

Characteristics of The 3 Muscle Fibre Types [Table]

Characteristics of The 3 Muscle Fibre Types [Table 2]

Metabolic aspects of individual muscle fibres form the basis of methods designed to determine percentage fibre type composition/proportions of whole muscles or muscle samples.

Skeletal muscle fibre typing: 1) The Muscle Biopsy

Muscles don’t have pain fibres so you don’t feel anything with the muscle actually being taken out, if you feel anything it’s related to pain receptors surrounding the other tissue.

Skeletal muscle fibre typing: 2) Muscle Processing

HISTOCHEMISTRY: Section, Stain, and Visualise using a microscope

GEL ELECTROPHORESIS: Homogenise and denature, Pass through gel, and Capture/separate MHC proteins

Motor Units

“A α-motor neuron and all the muscle fibres it innervates.”

Depending on the size of the motor unit they’re generally comprised of a similar size muscle fibre.

Motor unit characteristics

Low Recruitment Threshold = Easy to Activate

(unless we use these types most of the day for most activities unless we do higher intensity activities)

Motor units (the all or none principle)

AP 1:1 = if we’re stimulating the neurons were stimulating the muscle fibres

To change force output all we have to change is the number of neurons we activate – so activate more neurons you activate more muscle fibres within their specific motor unit

Henneman’s Size Principle

All the tissue is being recruited, you’re not switching off smaller slower motor units once you get to faster larger units. So training that recruits large motor units and FT fibres also develops ST fibre strength/hypertrophy because they are too being recruited.

Black  = muscle glycogen stores

Top Bar Graph 1: The diagram is demonstrating for long duration exercise @30% VO2 that glycogen is depleted from the ST T1 fibres first for the first 2 hours and then only after that do the T2a hybrid fibres glycogen stores get utilised because the T1 fibres are depleted. Only then does our body supplement our force production with recruitment of other fibres because our T1 fibres can no longer produce the force we need so the body looks to increase the recruitment of other fibres incrementally.

Muscle Fibre Type Distribution

Cross-sectional studies (Twins)

Each dot represents one child

We understand from this info the inference of how much genetic information contributes to fibre type makeup

The CSA and fibre proportion can indicate how the sport has influenced their fibre makeup and/or the type of populations that are gravitating towards certain sports because they naturally perform better at it.

Cross-sectional studies of fibre type in skeletal muscle

Cross sectional studies meaning you’re not comparing the same person twice, you’re comparing sample sizes to each other.

Which fibres/what % of fibres can transition to become other fibres?

It’s still unclear whether periods of training can convert fibres: have they changed one type of fibre into another type (e.g. type I > type IIa) or have they gotten rid of a specific type of fibres and grown new one’s of a new type in their place. Both?

Longitudinal studies (cross re-innervation)

On Rodent

In B) they cut the nerve and attached it to the opposite muscle and found the same muscle that was once either ST T1 or FT T2 now presented the opposite properties. Soleus(SOL) went from majority ST T1 (A) to majority FT T2 (B), the opposite was true for the EDL all by simply by attaching a different neuron to that muscle.

Part of the reason we get changes in the types of muscle fibres is simply due to the repetitive stimulation (APs) that we deliver to that muscle through the nerves that are attached to them. So were asking that muscle to do a particular type of activity, then that repetitive stimulation pattern will contribute to changing the type of muscle (fibre type expression) that we have.

Longitudinal studies (strength training)

Any type of exercise training induces adaptations of all aspects of muscle function per se, and is not limited to adaptations associated with the muscle fibre types

Strength Training

Variable results are dependent on the duration, intensity and specificity of the training

Improvements in strength occur through a variety of adaptations

Neural excitation of muscle (i.e. changes in the way the muscle is activated) via the pattern of motor unit recruitment and stimulation frequency. E.G. For novices in the early stages muscle fibre types are not changing much, the gain in strength is largely due to neural efficiency – i.e. the body becomes more efficient at activating muscle in specific motor patterns.

Muscle architecture via altered pennation and accumulation of SR and mitochondria

Muscle fibre hypertrophy:

As you expose a muscle to stress it experienced microscopic damage. In response the injured cells release inflammatory molecules called cytokines that activate the immune system to repair the injury. This is when the ‘muscle building magic’ happens. The greater the damage to the muscle tissue the more your body will need to repair itself. The resulting cycle of damage and repair eventually makes bigger stronger muscles as they adapt to progressively greater demands. However, without proper smart nutrition (amino acids), sleep and endocrine response your body won’t be able to effectively repair muscle damage.

an increase in muscle fibre size/cross-sectional area/diameter is the most significant long-term component contributing to strength gains because CSA is the single biggest determinant of maximal muscle strength (post)

We typically see strength training improve the intermediate TIIa fibre the most. But what type of volume/intensity/tempo etc are these studies doing to infer this?

Longitudinal studies (endurance training)

Generally more well defined and consistent muscular adaptations compared with resistance training Most likely due to relatively similar training load (intensity and duration)

Improvements in endurance occur through a variety of adaptations:

Oxidative capacity, via:

Angiogenesis (increased capillary development around all fibre types), and

Mitochondrial expansion (both volume and number, particularly in Type I fibres

Fuel storage (increased glycogen content of all fibres)

Muscle fibre atrophy (reduction in muscle fibre size/diameter) = why and how endurance activities contribute to smaller body composition

Combined with an enlarged capillary bed this muscle fibre reduction serves to improve diffusion, therefore: improve the supply of oxygen and circulating fuel sources and removal of waste products (CO2, H+, )

Initial changes (2 weeks) we see for endurance training are significant increases in mitochondrial activity and capillary development. What we don’t see is any change in the specific characteristics of the muscle fibres in the early stages. It’s only until we consistently train past 3-5~ weeks do we see other changes in the muscle fibre occurring at the SR and fast myosin decreasing which is the component that tells us that we’ve had a true change in fibre type for that muscle. If we stopped early at 2~ weeks it’s usually not enough time to make a change to the distribution of fibre type %.

---

Lecture 6: Exercise and Fatigue 1

Neuromuscular Fatigue

Fatigue: A reduction in muscle force or power output during exercise, which is reversible during recovery

Definition is based on a specific force criterion (e.g. power/speed/% of MVC)

Force Criterion: 100% or 50% Maximal Voluntary Contraction (MVC)

Black (left): Performing a 100% MVC at rest with no exercise done previously – to set baseline.

 Black (right): Perform exercise that produces fatigue, then re-test post exercise to see if they can produce 100% MVC at the same level of force. Obviously it can’t and we see that MVC force output is affected by about 30%.

White: We make the force criteria 50% MVC doing the same exercise as the previous experiment (black) – then we test again after exercise and see if they can perform 50% MVC to the same level of MVC. They can – so in this scenario, fatigue is not present.

^Sites of fatigue from a global view^

Fatigue serves as a protective mechanism for the muscle cells / CNS

Any motor activity begins at the motor cortex > sent down spinal cord > where we have an interaction with a-motor neurons which communicate to the muscle at the nueromuscular junction

Everything from the neuromuscular junction upwards is referring to the CNS

Central Fatigue

= Reduction in the capacity of the central nervous system to activate muscles

Complete recovery of muscle function may be incomplete for some hours, however, due to prolonged impairment in intracellular Ca2 release or sensitivity

After low-intensity exercise of long duration, voluntary force typically shows rapid, partial, recovery within the first few minutes, due largely to recovery of the central, neural component. (justification for LISS)

CNS Fatigue: Failure of NS to drive the muscle

You can have complete failure (rarely occurs) where CNS is not even sending signals to the muscle = the muscle will not contract.

What usually happens is a reduction in the number of signals being sent to the muscle, that COULD cause fatigue. We say ‘could’ because the signalling rate has to fall low enough to get below ‘tetanic fusion frequency’.

Tetanic Fusion Frequency = there is no more muscle summation (relaxation between each Hz stimulus) AKA the curve is smooth and there is no relaxation occurring – the muscle is in a continual contraction and you will get maximum force/stimulation. E.G. Diagram A) Soleus occurs at 50hz.

Top Right Diagram: If we are stimulating the soleus muscle at 200 hz and then we slow the frequency of stimulation in half to 100 hz as a result of fatigue, is that going to decrease force output? No – because the muscle we have not yet hit below the tetanic fusion frequency limit.

The lesson is here, yes during fatigue the driving frequency of stimulation to the muscle will fall, but it has to fall ENOUGH to get below the ‘tetanic fusion frequency’ before it affects force output.

Bottom Left Diagram: Fatigue has an influence on the tetanic fusion frequency – looking at the ST control figure, in a non-fatigued state you have to stimulate it at 50 hz p/s to get maximum force out of it. If that muscle is fatigued the frequency rate at which you have to give it to elicit maximal force is only 25 hz. The reason for that is because the relaxation rate slows down with fatigue.

A reduction in motor unit firing frequency occurs with fatigue, but slowing of this frequency (decreased neural stimulus) does not necessarily contribute to fatigue unless it falls below the tetanic fusion frequency. 

Mechanisms of CNS Fatigue:

1) Motor Cortex

Decreased central drive: neurons in the motor cortex become less excitable therefore they don’t project as many/or any signals down the spinal cord

Transcranial stimulation

Increased force during voluntary fatiguing exercise

Decreased central drive mechanism is unclear, possibly:

Inhibitory input from muscle mechanoreceptors and/or chemoreceptors to motor cortex which reduces it’s drive to the muscle = force reduction

Excessive increase in body temperature can effect mental motivation

Circulating metabolites entering brain eg. ammonia, tryptophan – these metabolites can affect brain function and central drive

Decreased blood glucose

2) Afferent Feedback

Another cite of failure/inefficiency can occur in the input which comes from the periphery back to the spinal cord. We have to have these α-motor neurons excited and sending info to the muscle for the muscle to contract. If we don’t have these α-motor neurons excited muscle contraction is adversely affect or not present.

Decreased excitatory input back to α-motor neurons from muscle mechanoreceptors (e.g. stretch receptors) – if these mechanoreceptors no longer send information back to excite the α-motor neurons less excitatory info is going to the α-motor neurons. Under fatigue these mechanoreceptors may not send as much excitatory info back therefore α-motor neuron drive decreases = less excitatory signal to the muscle = force reduction.

Increased inhibitory input of α-motor neurons from chemoreceptors measuring K+, H+ levels – chemoreceptors are measuring/looking for signals of metabolic stress. If they detect an excess of these by-products (H+/K+), the chemoreceptors will send info back to the brain where you may feel the sensation of discomfort/pain + inhibitory information will be sent to the α-motor neurons to decrease muscle contraction.

3) Lower or α-Motor Neuron Activity

Excitatory activity is depressed (less excitable) at spinal cord

Mechanism unknown

4. and 5. Action Potential Propagation (N/A for humans)

Once α-motor neurons are excited they start sending APs down, there’s no guarantee that signal will get to the neuromuscular junction – you could have failure of the propagation of the AP along the axon.

Failure to conduct action potential along α-motor neuron or at neuromuscular junction

Neither are sites of fatigue in human skeletal muscle

Central vs Peripheral Fatigue

The term “peripheral fatigue” is typically used to describe force reductions due to processes distal to the neuromuscular junction, whereas those due to processes within motoneurons and the central nervous system are commonly known as “central fatigue.”

Interpolated Twitch Technique is used to measure MVC and distribution of CNS/peripheral fatigue:

How it works: You create a MVC then you use a external electrical stimulus to stimulate the muscle on top of that. Once you hit the muscle with the external voltage your observing if there’s in increase in force or not – if there is, you know you’re not at 100% MVC, because if you were hitting it with an external stimulus should give you no further increase.

Pre-Exercise bar graph (left) can conclude that your driving 100% MVC because it stays even at 100% even with the electrical stimulus.

EG.1. Then you do a fatiguing exercise, you test if you can get 100% MVC again and it’s shown you can’t (black right bar). Then we hit muscle with voltage and it goes back to 100% MVC at pre-exercise levels. It couldn’t do that if the muscle was “stuffed”, but it has.Which means the CNS wasn’t driving the muscle fully 100%. So this drop in MVC force is due entirely with a problem with the CNS – it wasn’t driving the muscle maximally. So if all the MVC force is recouped with an electrical stimulus we know that all the fatigue was due to a CNS problem.

If the muscle is externally stimulated after a fatiguing exercise and it can’t produce any extra force and it stays the same, then we know this is due to a peripheral problem (muscle).

If we stimulate the muscle after fatigue and we get SOME of the force back (far right), but not all, the problem is due to a combined CNS + peripheral.

This is an important technique to determine the difference between central and peripheral fatigue.

Using this technique they’ve discovered the following…during

High Intensity Exercise

Exercise of less than 10 seconds = fatigue is peripheral (assuming it’s an acute fatigue response)

 If so, is the peripheral recovery from a maximal <10sec exercise determined by our energy systems? I.E. The ability of the ATP-PC system to replenish ATP (3~min for majority recovery)? Or something else as well? = Certainly recovery of PCr stores are important, but also recovery of muscle ionic disturbances (K+, Na+ and Ca2++) would also be involved.

Exercise that is greater than 10 seconds = fatigue is partly central: that central component can contribution up to 30% of the fatigue

Endurance exercise

Knee extensor MVC (A) and maximal voluntary activation (B) before and after an ultra-marathon:

Peripheral Fatigue

= Impaired muscle function, termed (Occurs only in muscle)

Primarily factors that influence:

Muscle Force or Tension

Contraction Time

Relaxation Time

What we typically see in a non-fatigued muscle in it’s contractile properties:

Need to remember terms: contraction time, peak force/tension, relaxation time

Muscle Twitch: the mechanical response to one stimulus

Isometric Twitch

For a isometric twitch, fatigue causes an:

IN in contraction time (taking a longer time to reach peak tension)

IN in relaxation time (longer go get back to rest)

Decrease in peak tension

Isometric Tetanus (Stimulating Rapidly)

Fatigue causes, decrease in peak tension

Isotonic Contraction (Muscle Shortening)

Fatigue, causes, a decrease in shortening (contraction) velocity and distance, and decrease in relaxation velocity (looking at the slope of the line, the control has a steeper line so the fatigue line is slower and control is faster)

Muscle Power

In fatigue, decrease in power

3 Factors to Muscle Force: *Post

1) Number of cross-bridges attached per CSA = how many myosin heads are attached and pulling on the actin. More heads that are pulling = more force.

2) Force produced per cross-bridge = just because a myosin head is attached to actin doesn’t mean it’s producing any force. The more force the myosin head is producing and the more that are attaching the more force you produce.

3) Duration of cross-bridge attachment

Fatigue is characterized by decreased force, therefore, one or all of above factors must be altered by fatigue

Contraction (or shortening) time is determined by:

1) Rate of cross-bridge cycling = how quickly the myosin attaches to the actin, pulls it, detaches and retaches again – the quicker the cycle occurs the quicker the contraction

2) Fatigue is characterised by decreased contraction (or shortening) time, therefore rate of cross-bridge cycling must be slowed with fatigue

Relaxation Time Is Determined By:

The rate of calcium (Ca2+) re-uptake to sarcoplasmic reticulum (SR) to activate the contraction

Fatigue is characterised by decreased relaxation time, therefore the rate of return of Ca2+ to the sarcoplasmic reticulum must be slowed

---

 Lecture 7: Exercise and Fatigue 2

Neuromuscular Fatigue

High Intensity Exercise

Sites of Peripheral Fatigue

1: When the muscle is about to contract a signal comes along the muscle membrane (sarcolemma)

2: That signal comes down the transverse tubule

3: And trigger the release of Ca2+ from the SR

4: The Ca2+ get’s released into the cytoplasm

5: Binds to the troponin

6: Allows the myosin head to attach to actin (we get the power stroke in force production) – to turn the whole thing off Ca2+ has to be taken off to troponin and pumped back into the SR

Each of these sties discuss different ways a muscle could fail under fatigue:

Peripheral Fatigue: Sites 1 & 2

Referring to the inability of a membrane to conduct an AP under fatigue. The main reason for this occurring is likely due to an excessive loss of K+ from the contracting muscle (during the re-polarisation phase). When you have thousands of APs occurring you can get a net loss of K+ from the muscle cell which causes the failure of the AP

Ionic concentrations (mM) across the sarcolemma:

A decrease in the K+ gradient across the membrane leads to a de-polarisation of the resting membrane potential

ICF = Intercellular Fluid / ECF = Extracellular fluid

K+ loss causes sarcolemma and T-tubule resting membrane potential to become depolarised.

During fatigue the resting membrane potential depolarises closer towards 0mV and that’s due to the loss of K+

The effect of this is that it’s more difficult to open up the Na+ channels which are required to get an AP

Depolarisation of resting membrane potential leads to de-activation of voltage-sensitive Na+ channels – No muscle action potential can be generated

Disturbances/failure in [K+] will be greater across T-tubules more so than in the muscle membrane

Small and relatively enclosed fluid volume in T-tubules

Due to small number of Na+/K+ ATPase pumps

Intramuscular K+ loss

Another thing to note why we’re getting this excess K+ with fatigue:

We may get comprised function of Na+/K+ ATPase pump unable to prevent loss – pump function may be compromised by decreased ATP supply

During intense contractions ATP levels within the muscle may fall so your energy supply to the pump may reduce so the pump function may be compromised. Therefore if this is not pumping so well your ability to get K+ back into to the muscle cell is reduced > more K+ is lost > more depolarisation of the membrane > less activation of the Na+/K+ pumps

Another problem that is occurring to allow for this excessive loss of K+…

Loss of K+ may increase with opening of ATP or Ca2+ dependent K+ channels:

[ATP] opens ATP-dependent K+ channels

­[Ca2+] opens Ca2+-dependent K+ channels

In a fatigues state these channels open and allow more K+ to leave the muscle cell. The ATP channel opens when ATP in the cell falls > more K+ is lost.

The Ca2+ dependent channels will open when you get an increase in Ca2+ concentration in the cytoplasm of the muscle cell

Peripheral Fatigue: Sites 3 & 4

Now assuming the AP has gotten down the t-tubule and has triggered the release of Ca2+, the next part where we can have failure is in the release of Ca2+ from the SR

So we can determine that the extra Ca2+ release from caffeine is not changing the muscle tension force produced in the pre and early fatigue state

Whereas late fatigue state drop off in force from early fatigue is due to a failure to release Ca2+, now why can’t we release the Ca2+…

A fall in ATP concentration and a rise in Mg2+ concentration will tend to keep this channel closed

Peripheral Fatigue: Site 6

With fatigue it is more difficult for the Ca2+ to bind to triponen

In a fatigued state you need more Ca2+ get produce the same amount of force

Peripheral Fatigue: Site 7

Cross bridges: Due to decreased force per attached cross bridge

Attached cross bridges can be in two states:

1) Weak binding, non-force producing state

  Actin/Myosin*.ADP.Pi

2) Strong binding, force producing state

  Actin/Myosin.ADP + Pi

(+ symbol represents inorganic phosphate being released  from the myosin head – when it does that then force is produced)

It’s harder to do this under fatigue because Pi concentration rises in intensely contracted muscle

Cross bridges: In early fatigue more cross bridges are in weak binding state

Probably results from increased [Pi]

Intramuscular [Pi] can increase 10 fold during intense exercise

Pi inhibits attached cross bridges moving from weak to strong binding state

Actin/Myosin*.ADP.Pi   →  Actin/Myosin.ADP + Pi

Peripheral Fatigue: Site 5???

How quickly can we turn a muscle off and get it back to it’s resting state – this relaxation rate is slowed with fatigue

What’s the consequence of this? If you can’t turn a muscle off quickly and it’s still producing tension, coordinated contractions are adversely affected.

Inorganic Phosphase (Pi) is playing a role in reduction of Ca2+ release, reduction in muscle force and slowing the relaxation rate. Pi is a major fatiguing metabolite.

Prolonged Exercise

There is a strong relationship (correlation) between time to fatigue and the amount of glycogen you have in your muscle for 60-85% endurance=type exercise intensity.

E.G. 4-5 hours of prolonged PA @ 60-85% VO2 requires over half a kg of stored glycogen

Research from the Centre for Human Nutrition at the University of Colorado that claim “glycogen (CHO), storage capacity is approximately 15g/kg of body weight” *Post

Why does more glycogen in your muscle allow you to go for longer…

If you have more glycogen in your muscle you have more ‘fuel’ to sustain high oxidation rates. We cannot break down fat and protein fast enough to produce ATP fast enough to maintain the exercise intensity. Hence they say CHO are required to maintain high oxidation rates and produce ATP fast enough. That is the THEORY.

What about high fat low carb keto type diets and their influence on supporting high oxidation rates with ketones?

UNTRAINED PEOPLE: In untrained people we see this ‘energy crisis’ of ATP levels in the muscle dropping once you can’t maintain the work rate anymore. Which supports the hypothesis that CHO are essential to maintain high oxidation rates.

TRAINED PEOPLE: But in trained people we don’t see any change in the the fall of ATP levels in the cells, they still fatigue over a longer time period and glycogen is till being used, but there’s no energy crisis which counters the theory suggesting that it may NOT be a fuel supply (CHO) problem.

Alternatively, in the trained people, fatigue possibly due to:

As glycogen levels fall they start to utilise fat and protein fuel sources, some of these fat and proteins that are being utilised are not best used for fuel. They may have other structural/functional roles to play, as you start to burn into those fuels the structural/functional roles they play could lead to fatigue of the muscle AKA Carbohydrate oxidation reduces fat and protein utilisation that are essential for normal muscle function

OR

Start considering that glycogen may not just be a fuel source, but play a role in structure:

Impairment of SR function:

– Destruction of Ca2+-ATPase Pump/glycogenolytic complex we know binds to glycogen molecules – when you take the glycogen molecules off the Ca2+ ATPase pump that pumps function is diminished

– Glycogen structurally important for normal function of Ca2+-release channels which can also have glycogen attached to them

OR

–Fatigue may be linked to, but not caused by lack of carbohydrate (it’s just a relationship, not cause and effect)

Other possibilities include prolonged exercise can cause:

Organelle damage of SR, mitochondria, sarcomere, triad structure

Central fatigue

---

Topic 2: Metabolism

Lectures 8 & 9 – Overview of Muscle Metabolism

Metabolism

The sum of all the chemical reactions occurring in a living organism

Catabolism – degradation

Series of reactions by which biological molecules are broken down into smaller molecules

These reactions often liberate ENERGY

Anabolism – formation

Biosynthetic processes in which cells form molecules from smaller units

Anabolism uses more resources/consumes more energy than catabolism.

ENERGY consuming processes

A biosynthetic process is more expensive than the reverse degradation process is lucrative.

Cellular energy (ATP)

When we break down ATP we’re left with ADP > AMP (adenosine myophosphate) > adenosine

Resting concentration of ATP is ~5 mmol.L and exercise concentration is very similar to each other which tells us we’ve always got the same amount of energy AVAILABLE to us when we’re exercising compared to at rest. We don’t really have a situation where there’s an energy crisis where ATP isn’t available. A lack of ATP doesn’t contribute to performance. Except during extreme high intensity exercise where the concentration can fall.

Aerobic Metaboism has the greatest capacity to produce ATP for exercise because it is the system that uses CHO/FAT for fuel which we have large supplies of, so its capacity to use it and generate fuel.

Energy (ATP) balance

The metabolic focus of exercise physiology is on:

The processes that produce and consume energy within skeletal muscle during exercise/contraction, and

The systemic mechanisms that support these processes.

Catabolic energy transformation (cellular metabolism)

Cellular energy consumption, and therefore, energy producing pathways are highly dependent on the characteristics of the work: i.e. in muscle, exercise: Intensity & Duration

The increase in energy consumption during exercise is distributed to:

Myosin ATPase  ~ 70%

Ca2+ ATPase  ~ 25%

Na+/K+ ATPase  ~ 5%

What are the things that contribute to this homeostatic appearance of ATP (constant concentration of ATP within the cell)?

Actomyosin ATPase: The cross bridge cycle where we have that myosin molecule grabbing that ATP and using it for energy (*most able to fluctuate level of energy expenditure)

Ca2+ ATPase pump: the process that removes Ca2+ from the cell and puts it back into the SR to cause relaxation (*mostly constant level of energy expenditure)

Na+ – K+ ATPase pump (*mostly constant level of energy expenditure)

These are the 3 biggest energy (ATP) consuming processes that we have within muscle.

Bioenergetics

The chemical processes involved with the production of cellular ATP

Muscle storage of ATP is limited

3 Bioenergetic Metabolic Pathways *Post?

1. Phosphagen system

Primarily encompasses cellular stores of ATP and phosphocreatine (PCr)

Therefore, also called the ATP-PC system

2. Glycolysis

Anaerobic breakdown of glucose or glycogen, often to form lactic acid

Therefore, also called the Anaerobic or Lactic Acid system

*Glycolysis System also contributes to aerobic metabolism so calling it anaerobic system is not entirely accurate.

3. Oxidative phosphorylation

Aerobic breakdown of fuels to form ATP

Therefore, also called the Aerobic system

1. The Phosphagen system

Anaerobic (i.e. provides ATP without using oxygen)

Occurs in the cytoplasm and includes the following:

Cytosolic stores of ATP

Resynthesis from phosphocreatine

Small amounts of resynthesis from other cytosolic reactions

The total creatine pool is small: 80% of the creatine pool at rest exists as PCr

Very powerful system: i.e. serves high work rates (e.g. 1000 W)

BUT

Capacity is limited (~ 5-7 seconds)

PCr formation requires ATP (reverse reaction), therefore: PCr reformation occurs primarily during recovery

Summary:

Everything about the Phosphagen system (P) occurs in the cytoplasm – we’re aware there are mitochondria in cells and they produce ATP, this system doesn’t happen in the mitochondria, it’s purely external to the mitochondria. P relies on stores of ATP and cellular stores of PC to resynthesize ATP from ADP and Pi.

P is catalysed by creatine kinase.

Short reactions like this typically occur quite quickly compared to longer chemical equations. Its fast and powerful but it’s capacity is limited.

Duration = 5-7sec~ which seems not as long as other places quoting higher 10-12sec amounts, but that’s because the capacity can be drawn out a little bit due to other energy systems contributing to produce ATP. But if you were to exclusively use PC it would be exhausted in 5-7sec.

Glycolysis

A common bioenergetic pathway for both anaerobic and aerobic metabolism of glucose. So glycolysis can be both aerobic and anaerobic depending on the PA duration/intensity.

Still occurs in the cytoplasm, which shows us the body has a great capacity to produce energy without mitochondria.

Provides an anaerobic source of ATP (considered a 10 step process)

During high-intensity work rates

Generally considered to last <30 seconds

These conditions often result in the formation of lactic acid from pyruvic acid. Lactic acid dissociates to a lactate anion (Lac-) and H+ which is what we measure through blood samples. It’s the H+ which are detrimental to exercise performance.

Therefore, the term “glycolytic” normally refers to aspects of anaerobic metabolism
…BUT…

Also provides the first phase of aerobic oxidation of glucose

We use glycolysis almost all the time, mostly when we’re doing low intensity normal daily activities which means no lactic acid build up. Remembering the final step in glycolysis is the formation of lactic acid.

For aerobic metabolism when we’re using glycolysis we don’t form lactic acid, we form pyruvic acid which is then used for ATP production in the mitochondria.

For aerobic/anaerobic metabolism for the glycolytic pathway the process is identical, except for the final product:

Final product for anaerobic glycolysis = lactic acid

Final product for aerobic glycolysis = pyruvic acid

The complete oxidation of glucose

Glycolysis is a 10 step process

Summary of Diagrams:

This energy harvesting phase results in a net gain of 2 ATP molecules through glycolysis via each glucose molecule. From an energy perspective, this is a pretty weak return on investment (2 ATP) for a large 10 step process. So we need to be able to get something more out of this and we do that through aerobic metabolism later on.

The hexokinase reaction is very important because it traps the glucose (or rather its by-product) in the cell.

The PFK step is probably the most important step in glycolysis, it’s our regulatory step that helps speed up/slow down the process. E.G. If we’re producing lots of ADP and we need to try and maintain that concentration of ATP within the cell then we need to speed up glycolysis. The by-products of ATP will be used to speed up glycolysis and conversely glycolysis will be inhibited when we already have lots to use already.

Glycolysis (some key knowledge points)

Important Points:

We can get more out of glycolysis if we bypass the first step (glucose > 6 phosphate = Heksokinase reaction) by using stored forms of glycogen which saves 1 ATP (increasing the yield by 50% (previously 2 ATP)) which has implications to improved performance in having adequate stored glycogen. Question: Why wouldn’t the second more efficient process be used all the time? *besides when glycogen stores are depleted, or is the Heksokinase reaction only used during times when glycogen stores are depleted?

Hexokinase reaction

Glucose phosphorylated to glucose-6-phosphate

Now “trapped” within the cell – i.e. cannot be removed from cell by glucose transporters (GLUT)

Phosphofructokinase (PFK) reaction

Rate limiting step of glycolysis (P&H table 3.3, p.58)

Stimulated by:  ADP, Pi, ↑pH  (generated when ATP use and work rate is high)

Inhibited by:  ATP, PCr, ↓pH  (generated when ATP use and work rate is low)

Others also capable of some glycolytic control include: Pyruvate kinase, Hexokinase & Lactate dehydrogenase

The glycolysis balance sheet

Lactate production

1. b) Consider the factors that result in the accumulation of lactate in the circulation. Discuss how lactate is generated in the contracting muscle and what physiological factors drive the generation of lactate. Within this discussion also discuss where and how lactate is cleared from the circulation.

High work rates at high ATP demand that stimulate rapid glycolysis (via PFK) eventually causes the accumulation of lactate which is generated via the enzyme lactate dehydrogenase which converts to pyruvate, then to lactate, and generates NAD+ (a very important substrate in glycolysis) to permit continued glycolysis.

High work rates of activity cannot be sustained for long periods of time with high levels of lactate. These high levels of lactate produce high amounts of H+ making the blood and body more acidic. The body wants to buffer acid in the body and blood, so if it detects a high amount of H+, RBC will attempt to buffer those excess H+ with bicarbonate contained within our our RBCs. This eventually triggers an increased release of CO2 through the body which triggers changes in VE. We buffer acid in the blood by breathing OUT CO2. Lactate is removed from circulation by the liver and kidneys (Levraut et al.)

LDH avoids a high NADH:NAD ratio which slows glycolysis, by permitting a lower NADH:NAD ratio which speeds glycolysis. Effectively deceiving glycolysis into the belief that NADH is rapidly entering the mitochondria which in turn rapidly delivers NAD (effectively suggesting that aerobic metabolism is currently satisfying ATP demand).

Effect of lactate

Arguably induces some degree of muscle fatigue (see reading below)

However,

Intense exercise cannot be sustained with high levels of lactate

H+ competes for Ca2+ binding sites on Troponin-C > Limiting the number of attached cross-bridges and most probably therefore, force. *Post

Lactate measurement in blood is used:

• as an indirect indicator of muscle acidity
• as an excellent determinant of aerobic/anaerobic fitness
• to monitor recovery from exercise (somewhat pointless!)

The body wants to buffer acidity in the blood so if we accumulate lots of H+ RBCs will try and buffer the excess H+ with bicarbonate being carried via the RBCs. So we help buffer acidity in the blood by expiring CO2.

What determines lactate production is the work rate of exercise (intensity/duration)

It’s not just about providing glucose to help produce ATP, it’s also about providing the substrate NAD+  that enables that 10 step glycolysis process to continue. To get that NAD+ quickly so we can continue to use glycolysis quickly then we need a very simple quick step: if we have a lot of time, such as during aerobic metabolism where we don’t need that NAD+ to come back so quickly then we can take a different pathway. But if we’re doing it quickly, pyruvate, instead of going into the mitochondria it gets converted to lactate, in that process we get back one of the NAD+ molecules.  So using up those NADH molecules to get back our NAD+ through the conversion of pyruvate to lactate is the reason anaerobic glycolysis continues at high intensity work rates to maintain the high rate delivery of ATP to support high intensity activity. Alternatively if we have a low intensity work rate the NAD we have enters the mitochondria instead.

Lactate is probably not one the things that produces muscle fatigue, it’s the fact we have other things that go hand in hand with the production of lactate. And that the lactic acid disassociates to a lactate ion and a H+. It’s the H+ that’s produced in combination with the production of lactic acid that can have negative effects to muscle. This is one mechanism of how anaerobic glycolysis can effect force production because of the production of lactate ions in conjunction with H+. *Post

Reference rebutting this: lactic acid is an advantage/disadvantage during muscle activity.

Ref: Lactic acid accumulation is an advantage/disadvantage during muscle activity. J Appl Physiol 100, 1410-1412.

Summary: The end point of glycolysis being the production of pyruvate depending on the intensity/duration of exercise (how rapidly we need to return that NADH to the cytoplasm).

Lactate as a Fuel

Via gluconeogenesis lactate can be used as fuel by being transported by the muscle into the blood to the liver where through a process called the cori cycle (lactic acid cycle) it is then converted to pyruvate and then back to glucose which can then be released back into the blood stream so we can maintain blood glucose concentrations. *Post

The pyruvate dehydrogenase reaction

When pyruvate isn’t rapidly converted to lactate we send pyruvate into mitochondria > once it gets here it’s broken down by the pyruvate dehydrogenase complex > cleaves off a CO2 (waste product) > generates NADH molecule > left behind with Acetyl CoA molecule.

Entering mitochondria
(Pyruvate, Lactate, NADH, FADH2)

NB: MCT – monocarboxylate transporter (transfers lactate), pyruvate also via a Pyruvate/H+ co-transporter

NB2: Malate-aspartate predominates in heart; Glycerol-phosphate predominates in skeletal muscle

The Krebs cycle / Citric acid cycle

Acetyl CoA enters citric acid (krebs) cycle > we get out another NADH > generate another single CO2 molecule waste product > generate another CO2 (at this point we’ve completely broken down glucose into its single carbon units) > we get another NADH > we get a GTP molecule that produces an ATP molecule > FADH > NADH. We went through all of this to get 1 ATP (pretty inefficient). But we got a bunch of co-enzymes (NADH) along the way > these are the things that will generate ATP for us when we put those into the electron transport chain.

PDH and Krebs (key knowledge points)

The electron transport chain (ETC)

A simple chain of enzymes that sit within the inner membrane of the mitochondria. This is where we can harvest the energy from these co-enzymes (FADH/NADH). It uses that energy to re-synthesize ADP and Pi.

ETC: Some key knowledge points

ETC enzymes (cytochromes)

Harness electrons (e-) from NADH & FADH2

Passage of e- through the ETC pumps H+

From NADH and FADH2 Into the intermembrane space (outer compartment) Generates an electrochemical gradient for H+, between Intermembrane space (outer compartment), and Mitochondrial matrix (inner compartment)

Passage of H+ down gradient through ATP synthase Generates ATP + H+ combines with O2 and residual e- to form H2O

Protein/Glyocgen/Triglyceride (Fat) Metabolism Diagram

Overall reaction:   Glucose +6O_2+32ADP+32Pi → 6CO2 + 6H2O + 32ATP

Summary of Glucose Catabolism

The whole process yields 28 ATP molecules which is a lot more than the 2 ATP when we just went through glycolysis and Krebs cycle. It’s when we go through all the processes into oxidative phosphorylation do we see a large yield. This is the justified value of taking glucose through all these steps. But high intensity exercise won’t go through all these steps, it doesn’t have enough time to.

Summary of ATP production (via glucose catabolism)

*2.5 ATP per NADH / **1.5 ATP per FADH

Triglyceride Catabolism

12-18 Carbons is a lot compared to a 6C molecule of glucose. Imagine how much ATP we could get out of an 18C fatty acid. Then imagine how much ATP we could get out of a single molecule of fat given that each one has 3 of these 18 carbon chains connected. (The # of carbons tells you about the amount of ATP you will yield from it).

FAT Catabolic Processes

Lipolysis: initial process of TAG catabolism: Breaks the fatty acid chains from glycerol

Yields: 1 glycerol (enters glycolysis), and 3 fatty acids (enter β-oxidation) / Each delivers multiple 2C Acetyl CoA molecules with same yield as per glucose

After TAG is broken down, the glycerol CAN enter glycolysis. So we can get a little ATP from glycerol, but it’s not regular, it doesn’t always enter glycolysis – 25%~ if the time you’ll get ATP from it.

Glycolysis (partly)

Glycerol enters glycolysis at the “branch point”

As dihydroxyacetone phosphate → gycerol-3-phosphate

β-oxidation

Where we get a large amount of ATP from fatty acids.

Now we start to see the commonalities between glucose metabolism and fat metabolism. Glucose ended up as Acetyl CoA and ended up in the Krebs Cycle where we got minimal ATP but lots of co-enzymes (FADH/NADH). Now through B-oxidation we’re generating Acetyl CoA molecules and they can go into krebs cycle and generate a much higher yield of ATP.

4 step cycle which cleaves 2C from each FFA per cycle

Each cycle provides: One Acetyl CoA (2C) unit for Krebs cycle, and One NADH, and One FADH2 for the Electron Transport Chain (ETC)

Krebs and ETC (as per glucose catabolism)

Entry points for FAT catabolism

TAG going through lipolysis > glycerol that CAN enter glycolysis > lipolysis of fatty acids through B-oxidation within the mitochondria that generate our Acetyl Co  that go into the Krebs cycle.

An 18 chain carbon will generate about 90~ molecules of ATP for a single molecule of TAG compared to 30~ for glucose. So fat is very powerful for a high yield of energy.

NB: Glycerol enters glycolysis at the branch point by forming dihydroxyacetone phosphate which is then converted to gycerol-3-phosphate

NB2: beta oxidation of FFA produces AcetylCoA and 1 NADH and 1 FADH2 from each 2C chain cleaved. Most TAGs are 12-18 carbons in length.

 

NB: FFA transport into mitochondria is complex (see Brook, Fahey & Baldwin, 4th Ed – Fig 7-6)

β-oxidation of fatty acids

Summary of Metabolism

All 4 metabolic fuel source components can fill/maintain the pool of ATP for the demand that is being called upon by the muscle. Each one can fill it at different rates = depicted by the size of the pipe – the larger the pipe the greater the speed we can fill up the pool of ATP but each fuel source pool is a different size which dictates it’s duration of fuel source.

---

Lectures 10 – Methods for Studying Exercise Metabolism

Energy expenditure

All energy expenditure results in the production of heat.

Knowledge of energy cost is useful for:

• Assessment of fitness and performance
• Planning training activities
• Individuals in weight control programmes
• Allocation of physical workplace tasks

Techniques

Direct calorimetry: Measurement of absolute heat production

Indirect calorimetry: measurement of oxygen consumption (‘Gold’ standard for exercise)

Other techniques may be more logistically suitable: HR, Accelerometry, Activity diary

First performed by Antoine Lavoisier (1783). Correlated heat production and oxygen consumption.

How are Direct and Indirect calorimetry related?

Oxygen consumption

Calorimetry

Direct relationship between oxygen consumption and heat production

Are there small portable wearable tech that measure O2 consumption for energy expenditure yet?

The task for the exercise physiologist

To convert O2 consumed into heat equivalents, but the type of foodstuff being used as a fuel needs to be known

This may be achieved by using the RER

Respiratory exchange ratio: VCO2/VO2

If you just measure ‘work’ (internal (cellular)/external (actual movement) that is done we greatly underestimate how much energy expenditure has occurred. Producing ‘HEAT’ takes up the majority of total energy expenditure. So what we’re really trying to do is quantify heat production.

RER: Respiratory Exchange Ratio

Used to estimate the contribution of CHO and FAT to aerobic ATP production

Energy expenditure

Extensive research enables a generalist approach to estimating energy expenditure

More activity specific tables can also be developed for variable intensities and durations (see ref Tab 3.4)

Nuclear magnetic resonance spectroscopy (NMR)

31P NMR spectraa

The muscle biopsy

Arteriovenous differences
(the Fick principle)

VO2 = Qx(a-vO2)

a-v arteriovenous 

O2 consumption is often expressed as above because:

All blood flow (cardiac output (Q)) passes from the venous circulation to the arterial circulation via the lung

Therefore, oxygen consumption by the body is simply the difference in concentration between arterial blood supplying the muscle and venous blood taking blood away from that muscle

i.e. (a-v)O2 difference

multiplied by

Blood flow (or in the case of the entire body, the entire cardiac output)

The same principle can be applied to any organ if:

The blood flow can be measured across the organ, and

The substance of interest can be measured in both the arterial input and venous output from the organ

Oxygen consumption
(the Fick principle)

a-v Differences across muscle
(an example)

Use the following to determine the rate of muscle glucose uptake.

a-v Differences across muscle

Advantages

Can precisely target exercising muscle as opposed to whole body metabolism as determined, for example, at the mouth.

Most certainly outweighs disadvantage noted below

Disadvantages

Highly invasive

Requires highly skilled surgical staff

Blood flow measurement is technically difficult

Requires expensive apparatus

Not able to categorically state the uptake/efflux is from skeletal muscle

Other organs perfused by the same circulation

e.g. bone, non-exercising muscle, resident adipose tissue, circulatory and interstitial tissues

Summary

A variety of techniques are available to investigate exercise and muscle metabolism

Consideration must always be given to advantages/disadvantages of each technique.

The value of research techniques are usually determined by 3 key factors:

Accuracy of the technique

Whether it is a direct or indirect measurement

Invasiveness of the technique

$ Cost

---

Lecture 11: Anaerobic Metabolism

Evidence of anaerobic ATP production

Graphs show contribution of anaerobic (red) and aerobic (white) to providing ATP for light vs heavy exercise.

Aerobic metabolism is the dominant pathway of ATP production during most exercise situations. However, anaerobic ATP provision plays an important role as an energy buffer when aerobic ATP provision cannot meet the demand for ATP. This occurs most commonly during the onset of exercise at all power outputs, when increasing the power output to a higher power output, and during intense or sprint exercise.

At the start of exercise there is always a contribution from anaerobic metabolism, which is when the O2 deficit occurs, then IF intensity stays constant we eventually get to a steady state. Unless we’re performing high intensity PA where a gradual increase in intensity occurs, this is where we’ll see O2 debt grow larger and a steady state not reached. This O2 deficit is what contributes to EPOC.

Interestingly EPOC only lasts 20min after 6min of high intensity supramaximal activity. I previously thought EPOC lasted for 24-72h. How much high intensity PA do you have to do in one bout for that to occur?

Oxygen Uptake Kinetics

At the start of exercise and during any sudden increase in exercise intensity, oxygen consumption and therefore, aerobic ATP supply, lags behind the ATP demand

VO2 Steady State = All ATP is being supplied by Oxidative Phosphorylation (the aerobic system)

Incremental Exercise

Demonstrating how increasing intensity during bouts of steady state activity requires an O2 deficit to take place

Energy Demand

Supramaximal Exercise

Sprint exercise is sometimes called ‘supramaximal exercise’.

Supramaximal Exercise
(the Wingate anaerobic cycling test)

What are the expected metabolic outcomes of supramaximal exercise?

Examination of the effects of 30s supramaximal exercise bouts

Phosphagen fuel

Phosphocreatine kinetics

Showing how much PC stores recover during repeated sprint bouts with 20/30/40sec recovery between bouts. Looks like we get about 15%¬ PC recovery with 20sec > 20%¬ PC recovery with 30sec > 25%¬ PC recovery with 40sec.

Adenine/Purine nucleotide balance

NB: total adenine nucleotide pool may be reduced by generation of IMP. IMP catabolism results in a loss of adenine nucleotides to the circulation, so muscle must begin a resynthesis process to restore the pool and therefore ATP concentration. Requires ~24-48 hours following repeated sprint training. If not maintained, [ATP] may fall from 5 mmol to 4.2-4.5 mmol.

Glycolytic fuel

Given the 1:2 ratio of glycogen to lactate in the equation, a 50-70 mmol.kg-1 decline in glycogen corresponding to 80 mmol.kg-1 increase in lactate, suggests there is still some aerobic metabolism of glycogen even during high intensity sprint exercise. As determined in Prac 5 this might be anywhere from 30-50% of the energy requirement for sprint exercise, but of course contributes more and more as the 30 s of exercise continues and anaerobic metabolism contributes a reduced amount.

Anaerobic contributions to supramaximal (sprint)exercise

Aerobic/Anaerobic Contribution to Supra-Maximal (Sprint) Exercise

 

Bar graph: What’s interesting is the contribution of anaerobic metabolism is relatively constant no matter the distance (total time) from 200-1500m which tells us that anaerobic metabolism is a finite.

What is the energy system contribution to an ‘all out’ 60 second exercise bout?

Technically, all 3 energy systems operate concurrently, however the relative contribution of each energy system is largely dictated by the type, duration and intensity of exercise. In the example of an all out 60 second sprint, the anaerobic pathways plays a dominant role as an ‘energy buffer’ because the aerobic system cannot meet the demand for ATP. We see this occur frequently at the onset of exercise and/or during high intensity short activity, such as a sprint. However, as shown in the diagram (Spriet, 2006) below, aerobic contributions rapidly increase once the 30-60+ second mark is hit with approximately 49% energy contribution derived from the aerobic pathway at the 60 second mark. While the 0 – 30 second time frame is the period where the large majority of energy is derived from anaerobic pathways.

Aerobic contribution to perceived anaerobic exercise

Simply showing aerobic energy system contribution during maximal intensity exercise (cycling) – we observe as power decreases and fatigue sets in aerobic contribution increases.

Same principle except demonstrating over a bar graph incrementally.

Anaerobic metabolism between fibre types

 Table showing how much ATP/PC/glycogen is depleted from each fiber type and in what quantities.

 Showing and reminding us that type 2 fibers aren’t the only fibres that contribute to sprint exercise. Remembering they’re recruited last because we always recruit smallest to largest in order to recruit as much tissue as possible.

Metabolic adaptations to sprint training

UT = untrained / Tr = trained

As we would expect peak and mean power increases (across a 30sec Wingate test) – practically this means we can produce more power and maintain it for longer which makes sense as an obvious outcome of sprint training.

Right diagram: Rest-exercise = the difference from pre to post exercise.

Over a 30sec sprint bout we see the Tr group get less of a reduction in the concentration of ATP and IMP. So we see the metabolic capability of the tissue much more efficient at providing ATP rapidly and sustaining it over 30 sec  

Why the improved ATP balance?

PCr ?

• Appears critical to short-term exercise performance, but muscle stores are limited and change little with training
• Creatine supplements may enhance PCr storage
• Enhanced CK activity may provide greater initial ATP production rate

Aerobic ?

• Possible increase in aerobic ATP production thereby conserving/prolonging anaerobic contributions via increased mitochondrial efficiency
• Small increase in maximal oxygen uptake (VO2 max)

Glycolysis ?

• Likely candidate given
• Greater (20%) lactate production
• Increased PFK activity
• Enhanced muscle buffer capacity against ionic imbalance and lactate

Identify and describe how skeletal muscle adaptations improve repeat sprint performance? *Post

Muscle Enzyme Activity

The largest improvement in sprint training comes through improvements of glycolysis through PFK.

Muscle Lactate & pH

Most wouldn’t expect a sprint trained athlete compared to untrained athlete to produce more muscle lactate following sprint training. Thing is, while a trained person produces more lactate compared to untrained, the muscle pH doesn’t get as acidic. So while lactate arguably doesn’t have much effect in muscle, the H+ do. While we see more lactate in TR we don’t see a greater build-up of acidity.

Why does a sprint trained person have lower muscle pH (acidity)?

Because a more highly trained person is able to buffer that acidity (H+) – they have a more efficient muscle buffer capacity (glycolysis efficiency is improving).

Sprint Training

Showing that we get mitochondrial/capillary development with both aerobic and anaerobic (sprint) training.

Tolerance to metabolic acidosis (muscle H+ buffering capacity) is possibly one of the biggest factors responsible for improving sprint performance over time.

ATP resynthesis rate

Our capacity to improve sprint performance and maintain that ATP pool (black) from sprint training comes largely from an improved efficiency in our capacity to use anaerobic glycolysis.

Why do we have the improved glycolytic rate?

Muscle enzyme activity (effect of sprint training)

1.Slight increase in vo2 max – which shouldn’t be a surprise because we know there can be a large contribution to sprint exercise from aerobic metabolism if the duration exceeds 30 seconds. So we should expect vo2 to improve.

2. Phospogen system not significantly improved.

3.The largest improvement with sprint training comes through PFK (one of our regulatory steps in glycolysis) which is the largest improvement (40%~) in our capacity to use glycolysis because we have more and faster PFK within the muscle tissue

4.SDH is a component of the Krebs cycle (an aerobic enzyme) that we don’t usually see much change with

Muscle lactate and pH (effect of sprint training) *Post

Sharp RL, Costill DL, Fink WJ & King DS. (1986). Effects of eight weeks of bicycle ergometer sprint training on human muscle buffer capacity. Int J Sports Med 07, 13-17.

UT people generate LESS lactate than sprint trained.

Most wouldn’t expect a sprint trained athlete compared to untrained athlete to produce more muscle lactate following sprint training. Thing is, while a trained person produces more lactate compared to untrained, the muscle pH doesn’t get as acidic. So while lactate arguably doesn’t have much effect in muscle, the H+ do. While we see more lactate in TR we don’t see a greater build-up of acidity.

Muscle buffer capacity (effect of sprint training)

Because a more highly trained person is able to buffer that acidity (H+) – they have a more efficient muscle buffer capacity (glycolysis efficiency is improving).

Sprint Training

This may explained why we get a small increase in VO2 max from sprint training.

If we look at the post training box we see more green markers = more mitochondrial development.

Showing that we get mitochondrial/capillary development not just with aerobic training, but with shorter anaerobic training (sprint).

Summary (metabolic adaptations to sprint/resistance training)

---

Lecture 12: Hormones, Exercise & Metabolism

Fuels sources for exercise

Intramuscular

ATP stores

PCr

Glycogen

Intramuscular triglycerides

Extramuscular

Blood/plasma: Glucose, Free fatty acids, Amino acids

Adipose tissue: Stored triglycerides

Liver: Stored triglycerides, Stored glycogen

Note: the body not only uses glycogen within the muscle and liver but also uses glucose in the blood/plasma (previously thought it only used glycogen)

Fuel contributions to exercise *Post

Powers & Howley, ANZ edn – Fig 4.14 and Fig 4.15

Bar Graph: 25% VO2 = walking~ pace

In the context of exercise INTENSITY:

We know and can see that during low intensity PA (25%~ VO2) that fat is used predominantly as a fuel source. Specifically Plasma FFA (coming from the circulation).

As we increase intensity a higher proportion of muscle glycogen and plasma glucose is used as a fuel source as plasma FFA proportion decreases.

In the context of DURATION:

The use of muscle glycogen as a fuel source starts to fall as duration increases and the largest fuel source that we’re relying on for longer duration exercise becomes Plasma FFA

*also assuming the intensity working at is about 75% VO2 max given that the distribution of CHO:FAT is about 50:50 (RER) upon onset of exercise.

Why does the contribution of plasma fuels decrease and muscle fuels decrease?

As exercise continues we get a gradual depletion of muscle glycogen, because we’re getting this depletion of muscle glycogen we need to maintain blood glucose concentrations otherwise the muscle will then keep drawing glucose from the blood stream – we’re running out of glycogen in the muscle, we have to get some glucose from somewhere, we’re getting it from the blood stream and if we keep pulling it from the blood stream blood glucose will decrease. So there are efforts made by the body to maintain blood glucose so there’s an increase in hepatic (liver) glucose output to maintain blood glucose. There’s also an increase in gluconeogenesis (production of new glucose from NON-CHO sources, e.g. lactate, )

How is fuel supply for exercise controlled?

Mobilisation

Transport into blood/plasma from: Muscle, Liver, Adipose tissue

Stimulation/Inhibition of:

Muscle, Liver, Adipose tissue

Breakdown/catabolism of:

Glycogen, Triglycerides, Proteins

Synthesis of:

Glycogen, Triglycerides, Proteins

Two Key Systems: Neural & Hormonal/Endocrine

SNS stimulates TG into FFA + the liver to breakdown stored glycogen and converts it to glucose and puts it into the circulation to be taken up by tissues

Actions of the ANS

Sympathetic

Neurotransmitter is noradrenaline which Innervates: Peripheral tissues & Adrenal glands

The Adrenal Gland enhances action by releasing catecholamines 1. Adrenaline (epinephrine), and 2. Noradrenaline (norepinephrine)

Generally, despite large increases in noradrenaline, it’s effects are limited to that released by the SNS onto tissues. Circulating adrenaline provides the effect of circulating adrenal medullary hormones.

Parasympathetic

Neurotransmitter is acetylcholine which innervates peripheral tissues (this function is less extensive than sympathetic). When the parasympathetic nervous system is activated, it releases acetylcholine to induce a low heart rate and a state of relaxation.

Reminder:

Insulin is the hormone that stimulates uptake of fuel into tissues

Glucagon is the hormone that stimulates breakdown of fuels and into circulation

Sympathetic ANS activity (intensity & duration dependent)

Powers & Howley, ANZ edn – Fig 5.16 and Fig 5.24

Right-hand panel measured at 60% VO2 max.

Intensities of 80-100%+ of VO2 have the largest and most rapid rises in adrenaline (epinephrine) but in any case lower intensity PA gradually increases both adrenaline and noradrenaline.

Increasing concentrations of circulating adrenaline is going to support mobilization of fuels.

Hormones that control fuel delivery and fuel use by contracting muscle

• Insulin & Glucagon (pancreas)
• Catecholamines (adrenal medulla):
• Adrenaline, and Noradrenaline
• Cortisol (adrenal cortex)
• Growth hormone (anterior pituitary)

Metabolic regulatory hormones during exercise

Flow Chart Diagram: IN in glucagon and decrease in insulin which act on the liver to help breakdown glycogen into glucose and put that glucose into circulation.

Pancreatic hormones

Insulin

• Secreted by β-cells of the pancreatic islets of Langerhans
• Promotes tissue storage/uptake of glucose, amino acids, and fat (particularly at rest)
• Remember: Insulin is a storage hormone, it wants to take fuels and put them into storage cites, it doesn’t want to release, it’s for that reason we have a suppression of insulin during exercise which allows for those fuels to be released into the blood stream.
• Decreases during exercise
• Contradictory to maintaining fuel uptake into contracting muscle

Glucagon

• Secreted by α-cells of the pancreatic islets of Langerhans
• Promotes mobilisation of fuels: E.G. Fatty acids from adipose tissue & Glucose from liver
• Increases during exercise
• Effectively assisting to maintain circulating fuel concentrations

Insulin during exercise DECREASES

Why? In order to prevent a rapid global systemic uptake of glucose by non-active tissues, THEREBY sparing blood glucose for contracting muscle, IF other mechanisms can enhance muscle glucose uptake

AKA “Insulin stimulates ALL tissues to take up glucose. When we exercise we don’t want all tissues to take up glucose, we just want muscle to take up glucose. So we take away the capacity for other tissues to access that fuel by reducing overall insulin, then muscle has a much better chance to be able to use that fuel if it has some other mechanism of taking that fuel out of circulation – and it does.”

In conjunction with glucagon: favours mobilisation (i.e. entry into plasma) of: glucose (from liver), and free fatty acids (from adipose tissue)

Controlled by: Increased sympathetic outflow during exercise, and Circulating catecholamines

As PA duration continues we see decreased insulin which blocks the uptake of glucose from the circulation allowing muscle to have access to more glucos from extracellular sources (plasma glucose)

Pancreatic control during exercise

Catecholamines (adrenal medulla)

Adrenal medulla

Considered part of the sympathetic nervous system: It secretes catecholamines 1. Adrenaline (epinephrine) 2. Noradrenaline (norepinephrine)

Catecholamines

Bind to receptors on effector organs – Both alpha (α) and beta (β) receptors

Induces changes in cellular activity via 2nd messenger systems

Catecholamines during exercise

One of the effects of blocking glucose entry into tissues is to IN FFA oxidation.

Blood glucose homeostasis during exercise

Controlled by fast acting hormones

Adrenaline and noradrenaline (adrenal medulla)

Insulin and glucagon (pancreas)

Maintain blood glucose by:

Increasing liver glucose mobilisation (glycogenolysis)

Increasing liver gluconeogenesis (glucose synthesis)

Increasing levels of plasma FFAs (adipose lipolysis) (Spares blood glucose and potentially muscle glycogen)

Limits muscle glucose uptake: Attempts to prolong/increase oxidation of FFAs / Muscle glucose uptake is stimulated via other mechanisms during exercise

Glycogenolysis: the breakdown of glycogen

Gluconeogenesis: the synthesis of new glucose via non-CHO forms – it does that through utilising amino acids, glycerol and lactate

Blood glucose homeostasis (via slow acting hormones)

Cortisol (adrenal cortex)

Contributes primarily to liver gluconeogenesis: Probable role in tissue repair following exercise rather than to directly influence blood glucose

During exercise it may also: Increase lipolysis & limit muscle glucose uptake

Growth hormone (anterior pituitary)

Contributes primarily to protein synthesis

During exercise it may also: Stimulate gluconeogenesis (Liver), mobilise FFA (adipose tissue) & Limit muscle glucose uptake

Unlike fast acting hormones, both cortisol and GH are influenced by a variety of stressors. E.G. cortisol mainly increases dramatically during heavy exercise (P&H p.96 Fig 5.11 for release pathway)

 

Summary (hormone response to exercise)

Balance is to:

Favour fuel mobilisation (both glucose and FFAs)

Limit tissue uptake (muscle serves itself)

Ensure circulating fuel supply for exercise

---

Lecture 13 & L14: Oxidative Metabolism of CHO & Lipid

Fuels during prolonged exercise

Oxidative catabolism of CHO & Lipids

Provides most of the energy to fuel muscle contraction

Exceptions:

1) During work rate transitions (inc. beginning of exercise):

During work rate transitions where we go from rest to an exercising state or change work load from one work load)to another, e.g. 60W – 90W on a bike or / 5 m/s – 7 m/s run. During this transition we see a lag in O2 consumption where it takes a short while to reach back to a steady state. This is a point which we use anaerobic metabolism to catch up to the energy requirements that we need until we can consume enough O2 and oxidise the fuels to contribute to that exercise.

2) At high-intensity work rates:

Above anaerobic threshold where oxidation of fuels still occurs but it’s supplemented of anaerobic pathways.

Amino acids

Derived from protein stores

Make a small contribution to ATP production (<10%)

Remember: tissues can synthesize new glucose from other means like lactate and amino acids.

Sources of CHO & lipid (for oxidative metabolism during exercise)

Diagram: Showing 4 fuel sources and how they’re processed and utilised: Showing glycogen being broken down to glucose – 6 phospote through glycolysis to pyruvate into citric acid cycle > we get our waste products (CO2/O2/H20) / Triglycerides within muscle can also funnel into process / Depending on the exercise intensity we can produce lactate which potentially be used as a fuel, not so much for contracting muscle but for other tissues. Lactate will get processed by the liver and/or inactive non-recruited muscle. / Liver can produce glucose which is transported into muscle. / Adipose tissue can break down into FFA > transported into muscle and utilized as fuel.

Relative contributions of CHO & lipids

Determined primarily by the interaction between exercise INTESNITY & DURATION

Also influenced to some extent by: training status and pre-exercise diet

How Fasting Influences Fuel Expenditure Distribution: *Post

Fasting impacts circulating glucose which is lowers as you fast. When you try and perform exercise what we see for RER (respiratory exchange ratio – used to estimate the contribution of CHO and FAT to aerobic ATP production) compared to someone who is not fasting, is your RER decreases to a level that indicates more fat metabolism (e.g. <0.8~) than CHO metabolism. But as soon as you eat again (especially if it’s a CHO rich meal) blood glucose raises back up again > your RER increases (0.90>). This simply demonstrates one mechanism of how diet/nutrition status influences the fuel type distribution during PA.

Exercise intensity and fuel selection

Low-intensity exercise (<30% VO2max): primrary fuel = fat

High-intensity exercise (>70% VO2max): primrary fuel = CHO

‘Crossover’ Concept

Describes the shift from fat to CHO metabolism as exercise intensity increases

Occurs due to: Recruitment of fast muscle fibres & Increasing blood levels of epinephrine

The increase in adrenaline (epinephrine) contributes to the increased CHO utilization during exercise.

Exercise intensity and fuel source

Training Status: Some people are much more efficient at utilising particular fuels when they’re highly trained vs. untrained.

Exercise duration and fuel selection

During prolonged exercise there is a shift from CHO metabolism toward fat metabolism

And we see an increased rate of lipolysis: Breakdown of triglycerides into glycerol and FFAs stimulated by rising blood levels of epinephrine

The shift from CHO to fat metabolism during prolonged submaximal exercise

Exercise duration and fuel source

 

Muscle glycogen utilization

The rate of glycogen breakdown is proportional to exercise intensity

High-intensity exercise = rapid glycogen depletion AKA High Intensity Exercise shows very large rates of glucose uptake into muscle some 4-5x than what they are at rest.

Low-intensity exercise = slow glycogen depletion

The extent (i.e. total amount) of glycogen depletion is also therefore partly related to exercise duration

Short duration exercise = limited glycogen depletion despite intensity that produces a rapid rate of glycogen utilisation AKA we use glycogen quickly, we just don’t deplete very much of it because of the limited duration.

Long duration exercise = limited glycogen depletion: Intensity that produces a slow rate of glycogen utilisation despite being maintained for an extended duration AKA when we drop the exercise intensity for long periods of time (e.g. <30% VO2) the requirement for CHO goes down and FAT goes up therefore our rate of glycogen utilisation is small so the total amount of glycogen being depleted is very slowly as time goes on.

Medium duration exercise = maximum glycogen depletion: Intensity that produces a rapid rate of glycogen utilisation that can be sustained for a moderately long duration

Glycogen depletion during exercise

Graph: The steeper the line the faster the rate of glycogen depletion. Pink boxes indicate % of VO2 max.

Glycogen depletion is thought to be a considerable factor to contributing to fatigue for prolonged PA. Which is where CHO loading parameter’s come in for increasing the glycogen/glucose pool. Especially if there is an increase in intensity in prolonged PA – glycogen then becomes even more critical as it becomes a more predominant fuel source.

Muscle glycogen utilization

Major Factors

Requires inorganic phosphate (Pi)

Pi: The muscle is contracting using ATP, cleaving off a Pi so we have this change in concentration of our adenine nucleotide pool within muscle that’s contributing to glycogen utilisation.

Muscle glycogen catabolism is under dual control

1. Hormonal control (B-adrenoceptor stimulation by adrenaline) via cyclic AMP second messenger

2. Contraction mediated control (Ca2+-calmodulin)

Minor factors

Direct relationship between: pre-exercise glycogen stores and glycogen use

Increased plasma FFA reduces muscle glycogen use

Debate over whether increased plasma glucose availability spares muscle glycogen

Debate: Drinking glucose put’s the blood glucose concentration up so the muscles got access to more glucose. When you do that and are considering the concept that if you give the muscle more glucose in the circulation it will use less of its stored glycogen – the majority of scientist don’t believe that – that providing glucose doesn’t spare glycogen. It does improve performance which is another topic, but it very likely doesn’t spare glycogen.

Control of glycogenolysis

As soon as we start a muscle contraction, the concentration of CA+ increases but the concentration of adrenaline in the circulation is still normal, it takes some time to increase. There are 2 factors here that contribute to glycogen utilisation, one being CHO going through glycolysis and then later in during exercise where we get a change in hormonal concentration which can help fine tune the requirements for that glycogen utilisation/breakdown.

Muscle glucose uptake(exercise intensity & duration)

Mechanisms that cause an increased muscle glucose uptake

Within the cell membrane we have these glucose transporter protein

GLUTE 1: in all cells of the body (impacted by insulin) – so it will be transporting less glucose into tissues under the conditions of exercise with the falling insulin concentration

How does fuel get from the blood into the muscle. It need’s to be transported.

To get glucose from the blood into the muscle we need a transporter and that transporter is known as:

GLUTE 4: Exclusively expressed by muscle. Binds to the transporter and pushed to the other side of membrane to be utilized.

These glute 4 proteins are contained within muscle cells which are stimulated via muscle contraction and increasing levels of adrenaline – we  stimulate these vesicles to move to the surface of that cell and put those transporters into the cell surface membrane. This gives muscle an enormous advantage over other tissues by being able to take glucose from the circulation while other tissues cannot.

Summary: When we talk about muscle being able to take glucose out of circulation during exercise – it does this through inserting these transporters into the surface membrane occurring through 2 mechanisms: one CA+ driven and one via hormones (adrenalin). The result is transporting glucose across the cell membrane into muscle.

We can achieve an increase of glucose delivery to muscle in 2 ways

(Reference to 3rd dot point in slide above)

1. By increasing concentration in the blood. But as we’ve seen blood glucose concentration stays relatively constant during exercise.

2. Or we can simple increase muscle blood flow. We’re delivering not only delivering glucose but delivering O2 and generating waste products  (discussed more later).

3. Increased plasma glucose availability: Which is a justification for taking CHO during exercise.

Muscle glucose uptake

Insulin

NOT required for contraction stimulated glucose uptake, but indirectly enhances muscle glucose uptake during exercise

Increased plasma glucose availability promotes muscle glucose uptake e.g. via CHO ingestion 

Blood glucose homeostasis

Given contracting muscle uses plasma glucose additional glucose enters the blood to prevent Hypoglycaemia – blood glucose is critical for CNS (brain) function, and fatigue i.e. by maintaining fuel supply & potentially sparing muscle glycogen

The concentration of glucose in the circulation is critical for one main reason: to preserve the fuel supply to the bran.

Why We Maintain Glucose Homeostasis:

One of the biggest reasons we have glucose homeostasis when we eat food > insulin secretion > tissues uptake it > blood glucose is controlled very tightly in order to protect the brain because we know glucose can damage blood vessels in excess.

Liver

Produces and releases glucose into blood stimulated via

1. Sympathetic activity (inc. Adr/NorAdr from adrenal medulla) and

2. Increased circulating glucagon and reduced circulating insulin

Liver glucose output (exercise intensity & duration)

Diagram Summary: High intensities of exercise utilise the most CHO (taking more glucose out of the circulation). There’s a good match between muscle tissues taking glucose out of the circulation during exercise at a particular rate depending on the exercise intensity and the liver putting glucose into the circulation at that same rate maintain homeostasis and meet physical demands.

Diagram 2: Blood Flow Going To The Liver

Kjær, M (2006) Hepatic metabolism during exercise. In Exercise metabolism 2nd Ed.(Hargreaves M & Spriet L, Eds.) Fig 4.2, p.47. Human Kinetics.

Even though we have this good match between glucose uptake by muscle and glucose output by the liver this is in lue of blood blow falling as exercise intensity increases. We see it goes down to 20%~ of blood flow going to the liver at the high ends of %VO2 max. This is going to makes it more challenging for the liver to match that uptake of glucose.

Mechanisms regulating liver glucose output during exercise

1. Pancreatic hormones

Reduced plasma insulin & Increased plasma glucagon

2. Sympathetic activity

Increased to pancreas and adrenal medulla & Increased circulating adrenaline/noradrenaline

3. Cortisol

Promotes liver gluconeogenesis (synthesis of new glucose via non-CHO forms)

4. Other factors released from contracting muscle like interleukin

Interleukin’s are other things circulating around the blood during exercise that can stimulate tissues to put fuel into the blood such as interleukins. Interleukins show us that some muscle is an organ that can generate some hormonal activity without feedback with CNS therefore helping uptake of glucose.

5. Increased plasma glucose inhibits liver glucose output

Liver glucose output

Majority of liver glucose output is derived from liver glycogenolysis (breakdown of glycogen)

Liver glycogen stores:

are limited in size/capacity and when when depleted liver glucose output declines → hypoglycaemia

Liver glucose production (gluconeogenesis)

Can occur from non-CHO sources (i.e. amino acids) but this rate is slow.

CHO ingestion during prolonged exercise

via portal vein to liver maintains blood glucose and therefore a high rate of muscle CHO oxidation and delays fatigue

How Intra-Session CHO Fuelling Works:

Depends on event duration and intensity, may only be significantly relevant if PA is 1-2+ hours. Ingesting CHO intra-session to maintain levels of plasma (extracellular stores) of glucose but evidence is mixed as to whether CHO ingestion during long duration exercise does anything to slow down the depletion of muscle glycogen, but it may be helpful.

When we take in glucose during exercise it goes straight to the liver because all the substances we absorb through the small intestine travel through the portal vein going straight to the liver to be processed. The liver see’s this glucose concentration coming through the digestive system in tern influencing liver glucose output. Theoretically this can help delay fatigue by maintain circulating blood glucose and CHO oxidation.

Muscle glycogen and blood glucose use during prolonged exercise / fasting

Prolonged Exercise Diagram: *Post

Relevant to endurance athlete: how we can theoretically improve performance with CHO intake during prolonged PA.

Yellow: We can see as time goes on we get progressively less contribution of glycogen to that exercise bout partly because glycogen is being depleted so we supplement that with glucose from the circulation.

Blue: At the 2-3 hour mark we hit an inflexion point where struggle to utilise CHO from the circulation and very rapidly the ability to provide CHO from the circulation starts to fall around the 3h mark. This is where we see exercise halt.

Purple: On the other hand if we provide glucose prior and during exercise we can maintain that blood glucose concentration without relying solely on muscle/liver stores. We can see we’re able to continue on for longer at 70% VO2 max while mitigating fatigue compared to the fasted group.

FFA use during exercise *Post

Depends on exercise intensity and duration

With increasing intensity FFA release from adipose tissue declines, but muscle fat oxidation is maintained by intramuscular TGs

During intense exercise:

Both adipose tissue and IM lipolysis are inhibited

This Inhibition of adipose tissue lipolysis is possibly due to high lactic acid production (promotes TG storage)

Lactate is a stimulus to store fat – synthesise fat and store it away in adipose tissue. We start to generate a competing influence over fat metabolism at the adipose tissue level. Hormones like Adrenalin and glucagon signal to put FFA into the circulation but when we start to produce lactate that’s a signal for fat to start to store away FFA and synthesise TG.

Obviously FFA don’t contribute to energy expenditure as much as we might like. As exercise intensity increases we don’t utilise fat as much because it’s much more time consuming and difficult to utilise fat. So it’s this trade-off between the amount of ATP you can get from fat and the time available for being able to generate that ATP.

Remembering the diagram that showed the 25/65/85% intensity change we see an overall fall of fat utilisation as intensity increases but we also see a change in what gets used from the circulation vs the muscle. We see large amounts of FFA from the plasma being used at 25% VO2 but when you shift to 65% we see a much greater increase in the amount of TGs being used from within muscle and a greater fall in the amount of plasma. Of course when you go to even higher intensities both of these decline. *Post (what’s the practical implication of this for fat loss – what do you want more of?

Control of FFA release (from adipose tissue)

Depends on rate of TG lipolysis catalysed by hormone sensitive lipase (HSL)

Major factors promoting HSL activity and lipolysis:

1. Decreased circulating insulin

Decreased circulating insulin could be an argument FOR controlling insulin secretion spikes (mitigating insulin resistance) via a lower CHO diet if fat loss is a priority? (for the goal of decreasing HSL > improving efficiency of TG lipolysis).

2. Increased circulating catecholamines (which act on B-adrenoceptors)

3. Glucagon also promotes HSL activity and lipolysis to a lesser extent

FFA release is also affected by:

1. Lactic acid production (promotes TG storage)

2. Adipose tissue blood flow

We can actually remove blood flow completely from adipose tissue during high intensity exercise. If you’re trying to provide fuel for adipose tissue for muscle at high intensity PA, its even more difficult given that we’re taking so much blood flow away from adipose tissue that we can even shut it down completely. This is another reason why we see lower intesnities of activity be much more efficient at utilising fat for fuel. *Post

3. Plasma albumin: FFA ratios (required for FFA TRANSPORT in the circulation)

Summary of FFA mobilization (adipose tissue)

Powers & Howley, ANZ edn – Fig 5.32

So we can see the 3 hormones stimulating HSL > which breaks down TG into FFA > they go off into the circulation and processed.

Falling insulin blocks glucose entry – if we decrease glucose entry than that’s a signal for adipose tissue to say there’s a fuel shortage so we’ll stimulate breakdown of TG to go into the circulation.

If there is lactate present it’s going into adipose tissue cells > stimulating re-synthesis of FFA with glycerol repeating a cycle until lactate diminishes (won’t entirely be confined to this repetitive cycle of FFA re-synthesis, you’ll still have some FFA going into the circulation).

Lipolysis: Adipose Tissue

What we see at low intensities of exercise is we’re using a significant proportion of FAT (plasma FFA predominantly).

You increase the intensity (65%) and we see a greater release of FFA release from adipose tissue.

When we go to 85% yet our FFA going out into the circulation remain the lowest at 15~.

Then when we halt exercise FFA start accumulating in the circulation which is interesting because that didn’t occur at the lower 2 intensities. The reason for this is because we have these large hormone concentrations in the circulation still and some other reasons he didn’t explain well.

We know that FFA can come from different places. They can be broken down from TG within muscle then used, OR we can take them from adipose tissue and put them into circulation and send them to the muscle cell.

Regulation of muscle lipolysis

Not completely understood

Muscle contains an isoform of HSL

This HSL activity may be controlled by: sarcoplasmic calcium levels, and adrenaline

IMTG content is reduced in Type I muscle fibres following exercise (fasted state)

Muscle FFA uptake

Initially thought to occur via diffusion

Recent results suggest: Carrier mediated process involving various FABP (fatty acid binding proteins), sarcolemmal, and cytosolic

FFA Uptake

Fatty acid transporter proteins are up-regulated during exercise (120 mins cycling at 60% VO2max)

Muscle FFA oxidation

FFA must enter mitochondria

Long-chain fatty acids transported into mitochondria via Acyl-CoA synthetase, and Carnitine palmitoyl transferase (CPT)

Fatty acids then undergo β-oxidation – B-oxidation being our: cleaving off our Acetly-Coa molecules > then put them into the krebs cycle > generate ATP.

Fat oxidation increases during cycling exercise (120 mins cycling at 60% VO2max)

Graph: We see the FFA oxidation increase over time as expected if you keep exercise intensity constant. We see the increase in FFA oxidation over time because the time gives an opportunity to fine tune your ability to oxidise fat.

CHO and FAT Interaction

Interaction between fat and carbohaydrate metabolism influenced by:

Substrate availability, Activity of key regulatory enzymes, Specific regulatory mechanisms are not completely understood

Summary

Demonstrating the speed of glucose metabolism: glucose moving into through a transport protein (GLUT4) into the cell > glycolysis > pyruvate (by-product that could produce lactate) > goes into mitochondria > krebs cycle

Fat metabolism there’s much more: need a lot more binding proteins > need to transport it everywhere > break it down through B-oxidation > krebs cycle

---

Topic 3: Oxygen Transport Systems

Lecture 15 & 16: Cardiovascular Responses to Exercise

Oxygen Demand

O2 demand by contracting muscles during exercise = 15-25 times greater than rest

At rest the average person consumes 0.25-0.3 L/min of O2.

Maximal Oxygen Uptake (VO2max) = Oxygen consumption plateaus despite increasing work rates AKA the maximum amount of oxygen a person can utilize during intense exercise.

VO2: When measuring VO2 it’s the volume of O2 consumed (this means: breathed in O2 > pumped via heart to contracting tissues > extracted the O2 at the tissue level and the mitochondria have utilised it to convert into ATP). The VO2 max measurement is not about how long you can go for, it’s how efficiently you can deliver O2 to tissues.

VO2 increases due

to:

1. Increased O2 extraction by active tissues

2. Increased delivery of O2 to active tissues

1. Oxygen Extraction

Increased O2 extraction by active tissues

Fick equation

VO2 = Cardiac Output x (a-v O2 difference)

Higher arterio-venous difference (a-vO2 diff) =

a-VO2 diff  = Tissue O2 Uptake

Amount of O2 extracted per volume of blood

Increased O2 extraction for aerobic ATP production

2. Oxygen Delivery

Increased O2 delivery accomplished by:

1. Increased Cardiac Output

2. Redistribution of blood flow from inactive organs to contracting skeletal muscle

Cardiac Output = Amount of blood pumped by heart per minute

It is a product of heart rate and stroke volume. Q or CO = HR x SV

Cardiac Output: Average = 5L/min 

Stroke Volume = Amount of blood ejected each heart beat

SV Average = 30-50mL p/b

Cardiac Output: Heart Rate

Cardiac output increases due to:

1. Increased heart rate & 2. Linear increase up to heart rate maximum

Parasympathetic Nervous System HR Control

via the vagus nerve slows HR by inhibiting SA and AV node

AKA the vagus nerve is partly responsible for facilitating the PNS and keeping the HR at rest.

The VN directly impacts the sinoatrial node (SA) which is considered the ‘pacemaker’ of the heart.

SA Node = every second~ we get a signal from the SA node that spreads an electrical impulse through the atria > through the ventricles > to cause the contraction to force blood through to the rest of the body.

At the onset of exercise for the HR to rise from resting to e.g. 100 BPM the body has to take its foot off the brake (parasympathetic withdrawal: physiologically this means minimising SA inhibition). That rise in HR (e.g. at the onset of exercise) is due to a withdrawal of parasympathetic/vagal tone. It demonstrates the concept that the body doesn’t need to physically stimulate the HR to rise upon the onset of exercise, it just needs to take the break off (minimise SA inhibition).

To continue for the HR to rise to higher % of VO2 max (e.g. 100-150 BPM) we need to accelerate the HR via the cardiac accelerator nerves which stimulate the heart to pace faster (also utilising hormones like adrenal to facilitate to this). *Post (Summary Below at ‘Cardiac Output: Heart Rate’)

Sympathetic Nervous System HR Control

via cardiac accelerator nerves increases heart rate by stimulating SA and AV node

Cardiac Output: Heart Rate

Low resting heart rate: Due to parasympathetic tone

Increase in heart rate during exercise: initialling increase due to parasympathetic withdrawal up to ~100 beats per min

Later increase due to increased sympathetic nervous activity stimulation (Also regulated by other factors: Adrenaline, Thyroid hormone)

Cardiac Output: Stroke Volume

Cardiac output increases due to: Increased stroke volume

In untrained individuals we see an increase, then plateau of SV at around of their ~40% VO2max

In highly trained individuals we see continual increases in their SV but no plateau – this partly why explains the mechanism of how highly trained people can go for longer at higher intensities.

The max HR between a trained and untrained individual is similar, but the max cardiac output is clearly much higher in a highly trained individual than untrained. That’s mainly due to a greater SV at those higher workloads to therefore facilitate a higher cardiac output. *Post?

SV Influenced By:

1. End-diastolic volume (EDV) = Volume of blood in ventricles at end of diastole (“preload”)

2. Blood pressure = Pressure the heart must pump against to eject blood (“afterload”)

3. Strength of ventricular contraction = “Contractility” (contracting quickly or contracting quickly and more forcefully)

1. End-Diastolic Volume (EDV)

Frank-Starling mechanism (“more that comes in = more  that goes out”)

Greater EDV results in a more forceful contraction due to the stretch of ventricles + also dependent on venous return

Blood Pressure Changes Across The Vasculature

Showing the pressure differences in different components of the heart during a normal heart beat.

Systolic BP: The pressure exerted on the walls of the aorta during the contraction phase of the heart cycle.

Diastolic BP: The pressure exerted on the walls of the aorta during the relaxation phase of the heart cycle.

Venous return (rate of blood flow back to heart) increased by:

1. Veno-constriction

Controlled via SNS nerves that can control smooth muscle around those veins

2. Skeletal Muscle Pump

Rhythmic skeletal muscle contractions force blood in extremities toward heart

one-way valves in veins prevent backflow of blood

E.G. People who stand still for long periods often don’t get enough venous return and can get faint.

3. Respiratory Pump

Changes in thoracic pressure pulls blood toward heart as respiration increases

2. Blood Pressure

Aortic pressure is inversely related to stroke volume

High “afterload” results in decreased stroke volume:  requires greater force generation by myocardium to eject blood into the aorta in order to overcome increased resistance to blood flow that occurs during exercise

Reducing aortic pressure results in higher stroke volume

Blood Pressure Changes across the Vasculature

3. Strength of Ventricular Contraction

Enhanced by:

1. Circulating Adrenaline and Noradrenalin

2. Direct sympathetic neural stimulation of heart

Graph: If we increase the contractility of the ventricles via sympathetic stimulation which occurs during exercise we will see an increase in SV

Cardiac Output: Summary

Blood Flow* Post

Increases to working skeletal muscle

At rest  15-20% of cardiac output goes towards muscle

During maximal exercise that can rise to 80-85%  while decreases to less active organs (liver, kidneys, GI tract (splanchnic) and increase it to metabolically active tissues

Blood flow redistribution depends of metabolic rate (exercise intensity)

As cardiac output increases to 5x that of rest the majority will go to contracting muscle and RELATIVELY less blood will go to other areas. Important to note ‘relatively because at rest the brain was getting 15%~ of 5L/min but now it’s getting 3-4%~ of 5x of 25L/min so it’s not receiving less blood flow.

The body is also receiving relatively 4-6x less blood flow to digestion/assimilation of food which is about the same absolute amount (if not slightly lower) of blood flow at rest (if my math is right). Practical Implication: Expand on point about eating before exercise and how blood flow limitations may restrict effective digestion. Or blood flow efficiency/inefficiency may explain why some people are able to down a cho/protein drink within 5-30min of exercise and feel absolutely fine and perform. *Post

Blood Flow

Skeletal Muscle Vasodilation:

the arterioles can open up in the contracting muscle without any signal from the brain to let more blood flow in

Auto-regulation

Blood flow increased to meet metabolic demands of active tissue due to changes in O2, CO2,  nitric oxide, potassium, adenosine, pH

Vasoconstriction to visceral organs and inactive tissues: Sympathetic nervous system vasoconstriction

A contracting muscle releasing vaso-active substances (K+)

Summary: So the less active tissues vasoconstrict to help preserve blood pressure and the active tissues vasodilate via releasing these vaso-active substances to override the sympathetic vasoconstriction. So we have this great mechanism over getting O2 blood flow to contracting muscle and decreasing blood flow to areas that need it less during PA.

Plasma Volume and Exercise

You expand your blood volume and blood plasma via repeated bouts of training (chronic adaptation)

Plasma volume decreases (10-15%) at onset of exercise (acute adaptation) for the role of diluting the build up of metabolites (H+, K+, CO2 etc which want to draw fluid towards them)

With exercise we have: Increased capillary pressure > fluid moves into interstitium (the space between tissue and the blood stream) from circulation

Shift due to increases in capillary hydrostatic pressure and tissue osmotic pressure (exercise causes large hydrostatic pressure increase)

As exercise continues, further decrease in fluid loss due to sweating

Hemoconcentration: Plasma volume decreases during prolonged exercise

Heart rate and blood pressure adjustments minimise impact of reduced plasma volume on blood flow

Hormonal control: Anti-diuretic hormone (ADH) and renin-angiotensin system help maintain blood pressure and volume primarily by influencing Na2+ and water reabsorption at kidney

ADH (anti-diuretic hormone) helps conserve/hold onto fluid to mitigate the feeling of urinating during exercise. The body know’s it need’s to hold onto water during exercise so it has a mechanism to control that.

Oxygen Delivery: Summary

O2 Delivery: A product of cardiac output and the alteration/direction of blood flow to contracting tissue. How do we regulate cardiac output? = HR x SV. Sympathetic (adrenlain/noradrenlin) influences HR.

Cardiovascular Control

Initial signal to ‘drive’ cardiovascular system comes from higher brain centers

Central command (motor cortex – M1) co-ordinates activation of skeletal muscle and CV response

Message sent from M1 to CV control centre (medulla oblongata) in the brain directing it to modify cardiac responses in order to contract skeletal muscle. These cardiac responses will look like: increase HR, BP, vasoconstrict/dilate. It also receives information from various receptors to coordinate and modulate the CV response accordingly.

This sequence of responses can be summarised in the image below:

Efferent Signals (right): Carrying signal away from the brain

Afferent Signals (left): Carry signal towards the brain

Cardiovascular Control is fine-tuned by feedback from:

Chemoreceptors: Sensitive to muscle metabolites (K+, lactic acid)

Baroreceptors: Sensitive to changes in arterial blood pressure

Mechanoreceptors: Sensitive to force and speed of muscular movement

Mechanisms explain high precision between matching muscle blood flow with metabolic demands of muscle

Circulatory Responses to Exercise

Changes in heart rate, stroke volume and blood pressure depend on:

• Type, intensity, and duration of exercise
• Environmental conditions
• Emotional influences (adrenalin/noradenalin)

Rest to Exercise

At the onset of exercise:

1. Rapid increase in HR, SV, cardiac output

2. Plateaus during submaximal (below lactate threshold – the workload you can sustain) exercise

Rest to Exercise and Recovery

During recovery

Decrease in HR, SV, and cardiac output toward resting

Depends on: duration and intensity of exercise & training state of subject

3 Clear Adaptations to Endurance Training:

Lower resting HR, lower HR at a given workload and a faster recovery at HR back to resting post exercise.

Incremental Dynamic Exercise

Heart rate and cardiac output:

Increases linearly with increasing work rate

Reaches plateau at 100% VO2max which tells us we’ve reached our VO2 max.

A highly aerobically trained person can reach Q can reach 30-35 L/min

Systolic blood pressure

Increases with increasing work load because Q (cardiac output) is the main driver

Plateaus near maximum work load

Diastolic blood pressure

Remains relatively stable:

DP influenced by total peripheral resistance (how many vessels are opened/closed at different cites). During dynamic exercise (rhythmic movement: swimming, running, cylcing etc) total peripheral resistance doesn’t change much > therefore DP won’t change much and remains stable.

Vasodilation (active muscle) = vasoconstriction (other tissues)

May decrease at high intensities

Mean arterial blood pressure

Increases with exercise intensity and then plateaus

Prolonged Dynamic Exercise

Cardiac output is maintained despite decrease in SV

When anyone exercises they loose plasma volume: because we’re trying to draw in from the blood what we’ve lost in the interstition to make sweat so SV will decrease and HR will compensate by rising to maintain cardiac output. We call that…

“Cardiovascular Drift”

Due to dehydration and increased skin blood flow (rising body temperature)

Factors lead to reduced venous return

When we make sweat we draw fluid from the interstitial space towards the sweat glands > air flows over the skin > fluid evaporates > cools area underneath it and we thermoregulate.

The better trained you are: the more you sweat, the faster you sweat and the earlier you sweat – you  sweat more efficiently.  *Post

Some look over in the gym and see someone sweating a lot early in their workout – you might say ‘damn, their unfit look at how much their sweating’. Well, the better trained….

But how and why does this occur?

Endurance training is essentially a thermoregulatory challenge to the body. Muscles produce heat and the harder we push (ie when we are fitter) the greater the heat load that needs to be dissipated. Our body adapts to this by expanding plasma volume, improving blood flow to the skin for heat dissipation, and increasing the sweating mechanism required to cool the blood passing through the cutaneous (skin) circulation. This occurs at a lower core temperature in endurance training individuals, hence we sweat earlier, more (in terms of amount) and more efficiently when endurance trained. You need sweat produced, evaporation on the skin to cool the layer beneath it and increased cutaneous blood for efficient thermoregulation. This has less impact on the circulation as the plasma volume has already adapted. 

Source 1: Cardiovascular adaptations supporting human exercise-heat acclimation. Source 2:Influence of Aerobic Fitness on Thermoregulation During Exercise in the Heat

 

Static Isometric Exercise (Weight Lifting)

What happens to BP when you’re doing isometric contractions like weight lifting? This will cause SP/DP/peripheral resistance to increase.

Trained weight lifters have been measured to reach 350/250 BP – why don’t their blood vessels burst or they have a stroke? Because their bodies have progressively adapted to that pressure. But people can pop blood vessels in their eye’s via valsalva maneuver (especially people with hypertension who would be cautious do moderate – long isometrics/valsalva maneuver).

Occludes (blockage/closing blood vessel) muscle blood flow through the contracting muscle which increases activation of chemo-sensitive sensory nerve fibers in skeletal muscle

Feedback to cardiovascular control center “muscle chemoreceptor reflex” results in:

Increased cardiac output: Mainly due to increased HR & no change or decrease in SV

Exaggerated MAP increase: Increase in both diastolic and systolic blood pressure

---

 Lecture 17: Respiratory Response to Exercise

Respiration Overview

Exercise Intensity

Typical values for pulmonary ventilation (respiration) at rest and during moderate and intense exercise

Exercise Duration

VE (ventilation) increases rapidly initially, then slower rise toward steady state

PO2  and PCO2 only change slightly at onset of exercise and then remain stable suggesting that the increase in VE at onset of exercise is not as rapid as the increase in metabolism inferring that drive in VE has to be predominately neural, and not something in the blood

PO2 = partial pressure of O2 = the amount of oxygen gas dissolved in the blood. It primarily measures the effectiveness of the lungs in pulling oxygen into the blood stream from the atmosphere.

PCO2 = partial pressure of carbon dioxide = reflects the the amount of carbon dioxide gas dissolved in the blood.

Incremental Exercise

VE increases linearly up to ~50-75% VO2max then we see an exponential (alinear) increase beyond this point.

So VE is responding to the demands of exercise, but it’s not just the demand for O2 and production of CO2 driving breathing, there’s other factors at play.

“Ventilatory threshold” = the inflection point where VE increases exponentially (the black vertical thick line)

Control of Ventilation

How do we modify our neural control of breathing?

Via the respiratory control center: the medulla oblongata and the pons work together to:

FUNCTION:

1. MO regulates respiratory rate and depth

2. Receives neural and humoral (peripheral) input

Neural input

‘feedforward’ from higher brain centers (eg. motor cortex)

feedback from skeletal muscle mechanoreceptors

Humoral (blood-born) Chemoreceptors

Central Chemoreceptors:

Located in the medulla respond to changes in ↑PCO2 and ↑H+ in the cerebrospinal fluid stimulates ventilation

Peripheral Chemoreceptors

In the aortic and

bodies respond to changes ↓PO2, ↑PCO2, ↑H+, and ↑K+ in blood stimulates ventilation

Holding one’s breath causes O2 levels to drop slightly and CO2 to rise. The majority of people usually feel the urge to breath out after holding their breath due to the accumulation of CO2 which the body tries to expel via exhaling.

Regulation of ventilation is generally more sensitive to changes in blood PCO2 than PO2.

Left: We see a linear response between VE and the arterial PCO2 – so CO2 is driving VE. We see these sorts of changes in CO2 during exercise.

Right: If you measure the O2 concentration in your arteries at rest  = 100mmHg~. Even during exercise it shouldn’t drop too much unless you have some sort of pulmonary/CV disease. Hypoxic Threshold: When the body is exposed to hypoxia (low O2 levels at altitude) – the purpose is to increase O2 carrying capacity to improve aerobic endurance performance. Hypoxic conditions cause an increased respiratory rate because relative O2 levels are less than what your body has adapted to.

Or you could take the hormone EPO (Erythropoietin) to create more RBCs > improve O2 carrying capacity to improve performance and recovery

Submaximal Exercise

Primary drive: Higher brain centers (central command)

“Fine tuned” by:

Humoral chemoreceptors & Neural feedback from muscle

Higher Brain Center = M1 has an influence on respiratory control. We have central chemorecepotors responding to the CO2 and H+ (PH of the blood) and we’ve got peripheral chemorecepotors such as the aortic arch and the carotid sending signals back. We also have stretch receptors in the lungs to send signals to fine tune the breathing receptors.

The hypothalamus can also play a role in stimulating breathing. E.G. The hypothalamus  plays a larger role in stimulating breathing during extreme environmental conditions such as heat.

Heavy Exercise

Alinear rise in VE

“ventilatory threshold”

Underlying cause is unknown

One Possibility: ↑ blood H+ and CO2 from lactate stimulates chemoreceptors, called “lactate threshold concept” – AKA some people say the rise in breathing is caused by the rise in lactate/H+

Exponential (alinear) increase in ventilation,  other possibilities include:

• ↑ blood K+ levels stimulates peripheral chemoreceptors to stimulate breathing
• ↑ body temperature and catecholamines (when body temp rises hypothalamus can have an influence on breathing rate)
• ↑ neural stimulation from motor cortex and muscle receptors (greater motor-cortical drive to the respiratory control centre)
• There is no role for hypoxia that has been identified that occurs during high intensity exercise

Gas Transport

Showing that the O2 we breath (we breath in 21% O2 from sea level of 760mmHg which is total amount in the air), CO2 much less. + showing the distribution of gas transport from inhalation of O2/CO2 and how it’s trasnported through respiration

Oxygen Transport Carried In the Blood in 2 Ways

1. Dissolved in solution

• O2 not very stable (~0.3ml per 100ml blood)
• Amount dissolved described in units of partial pressure (PO2)

2. Bound to Haemoglobin (Hb) in RBCs

• Haemoglobin = Iron-containing globular protein pigment in red blood cells that transport O2
• Transports 4 O2 molecules per Hb molecule
• How much O2 is bound to the haemoglobin is known as ‘O2 saturation’ AKA O2 carrying capacity described as % saturation (0-100%)

Oxygen Transport In The Blood

The amount of O2 combined with Hb depends on how much is dissolved in plasma

Whilst the total amount dissolved in the plasma is small, it’s very important in determining:

Amount of O2 dissolved in plasma determines

Hb-O2 carrying capacity & Movement of O2 between lungs, blood and tissues

Hb-O2 Dissociation Curve

Graph: Top right part of the curve where the exchange occurs in the arteries you have lots of O2 binding to haemoglobin (nearly 100% O2 saturation). As you move the O2 on the haemoglobin through your circulation towards your tissues you offload about a quarter of what you got – as shown by the intersection with the ‘T’ dotted line. At rest ,the change in the partial pressure of O2 between the lunges (where’s there’s lots of O2 around) and the capillaries (where we get the exchange occurring) – because there’s less O2 at the capillary level haemoglobin wants to offload it, however when there’s lots of O2 available it wants to bind it. AKA at the lunges it wants to bind O2 and the tissues it wants to off load it.

Increases in temperature and/or decreases in pH with exercise result in curve shift to the right > Results in greater O2 off-loaded at tissues

AKA during exercise pH drops because H+ goes up > temperature increases which cause a rightward shift in O2:hemoglobin dissociation curve so that you’re more likely to offload O2 at the tissues and bind it at the lungs. How efficiently we do that influences our performance.

Myoglobin = muscle form of haemoglobin

Once we get the O2 to the tissues we need a different form of haemoglobin to take it from the outer part of the muscle cell to other tissues like the mitochondria. That’s where myoglobin come’s in:

Myoglobin binds O2 at lower concentrations and transports it to the mitochondria and offloads it there.

• Acts to shuttle O2 from cell membrane to mitochondria
• Similar structure to Hb
• Stronger affinity for O2 than Hb
• So it draws O2 from plasma/blood to muscle
• It gives muscle it’s red color – the more slow twitch a muscle fibre is the more myoglobin it has (remembering that we have more mitochondria in our ST fibres)

CO2 Transported in the Blood in 3 Ways

1. Dissolved in plasma (~10%)

2. Bound to de-oxygenated Haemoglobin (Hb) (~20%) (Carbamino-haemoglobin)

3. Transported as Bicarbonate (HCO3-) (~70%) (remembering: bicarbonate is a great buffer for H+)

• Red blood cells convert CO2 to HCO3-(bicarbonate) by carbonic anhydrase  (CO2 get’s transported as bicarb in the RBCs – a convenient efficient way to transport CO2)
• CO2 +H2O ↔ H2CO3 ↔ H+ + HCO3-
• Reversed in lungs

Exercise Training

Lunge size does not change measurably with endurance training (although we know our heart does) we just get more efficient with our breathing:

Mechanisms unknown: proposed mechanisms:

• Lower blood lactate?
• Less feedback from contracting muscles?
• Reduced central drive?
• Other factors, such as ↓ blood K+ and catecholamines?

 i.e. showing how one’s ventilation is lower at the same work rate following endurance training

Trained VS. Untrained

Ventilation threshold occurs at higher %VO2max

PO2 decreases (hypoxemia) at near-maximal

• ventilation/perfusion mismatch
• short RBC transit time in pulmonary capillary due to high cardiac output

How can ventilation limit our performance in highly trained athletes at very high %VO2:

 Because the cardiac output is so rapid in these situations, whatever you pump through the rest of the body it has to go through the pulmonary circuit. There is some suggestion that the transit time of the Hb through the capillaries is inadequate – so you don’t get complete saturation. Therefore you might get athletes displaying arterial O2 de-saturation at high work loads. This suggests that for this group of people they ventilation might be a limiting factor in their performance during intense exercise. This is one of the rare times we can see breathing limits performance (typically it’s due to cardiac output or disease)

Ventilatory Threshold (VT) & Lactate Thresholds (LT)

CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3–

The relationship between VT and LT is more coincidental, than causal. The VT appears to occur when we start buffering more lactic acid. However in the subset of people who lack the enzyme to produce lactic acid (lactate dehydrogenase) and when you observe their VE during exercise they still get the exact same response with their VE, therefore this relationship between lactic acid and VT is very likely not causal and more coincidental. Therefore if you want to accurately measure someone’s LT take blood samples which will tell you when lactate levels start to rise more presciently (which is why many recommend you not to rely solely on VE to tell you that). Changes in VE are driven by changes in CO2 and other factors, some people try and ascribe the ventilatory break points (2 vertical broken lines) to correlate with LT, I caution you on using that approach.

Remember: The exponential (alinear) rapid increase in VE (for intense exercise) is driven by the build of CO2, K+, Adrenalin, heat, greater motor-cortical drive – all these components that stimulate VE are more rapidly activating the neural control centre in the brain (medulla oblongata) to increase the rate and depth of breathing. 

Remember: Lactate (a lactate anion and a H+) – when lactate is produced (espeically during high intensity activity) it will produce a high amount of H+. The body wants to buffer acid in the body and blood, so if it detects a high amount of H+, RBC will attempt to buffer those excess H+ with bicarbonate which we have in our RBCs. This eventually triggers an increased release of CO2 through the body which triggers changes in VE. We buffer acid in the blood by breathing OUT CO2.

---

 Lecture 18: Physiological Determinants to Maximal Oxygen Uptake

Maximal Oxygen Uptake (VO2max)

VO2max describes the maximal rate at which O2 can be transported to and consumed by tissue

It’s not a measure of capacity, capacity = an amount. VO2 max is a RATE of O2 consumption per kg.

• At rest, VO2max: 0.2-0.3 l.min-1 (at rest VO2 influences BMR/ how well one can tolerate daily living activities)
• During exercise, VO2max: 3-6 l.min-1 (depending in fitness) (Equation = l.minx1000 / bw = ml/kg per.min)
• An excellent measure for someone’s potential performance
• Arguably a better predictor of your all cause mortality than BMI – e.g. fitness is now seen as one of the most important modifiable risk factors to cardiovascular disease

VO2 increases in proportion to exercise intensity

due to rise in:

• Aerobic ATP demand
• Cardiac output (Q)
• How much O2 you extract from the blood to mitochondria

 VO2 = Q x (a-v O2 difference) AKA VO2 = the delivery of O2 to contracting muscle x how much O2 is being offloaded to the tissues

Maximal Oxygen Uptake

 

A determining factor in endurance performance: GENDER

Cross country skiers generally score higher on VO2 tests because they are using more and larger muscle groups in their sport thus their body demands more O2 than runners.

Changes in response to training

Endurance athlete (65-85 ml.kg-1.min-1): potential for improvement is small (<5%)

Recreational athlete (35-60 ml.kg-1.min-1): potential for improvement (15%)

Inactive (30-40 ml.kg-1.min-1): Potential for improvement is larger (25-40%)

Measurement of Maximal Oxygen Uptake

Exercise mode

• Should employ large muscle groups
• Specific as possible to athlete’s sport (e.g. cyclist = on a bike / runner = on a treadmill / swimmer = in the pool)

True VO2max

• A true VO2max occurs when you are still increasing in work rate despite levelling off in O2 consumption AKA achieved if plateau in O2 uptake with increase in workload
• If there is no plateau = VO2peak (which tells you the person definitely has more in them to go harder)

Other indicators of VO2max

• blood lactate >8 mmol.l-1
• RER >1.10 (100% glycogen)
• HR within 10 bpm of predicted maximum HR

Measurement of Maximal Oxygen Uptake

Can be determined directly or indirectly

Direct measurement of VO2max:

• Usually performed in a laboratory
• Performed on motorised treadmill or cycle ergometer (a variety of ergometers can be used eg. rowing ergometer, swimming flume) – Ideally try to replicate movement patterns of sport

• Often an incremental test (upping workload per minute) until volitional fatigue
• Expired air is measured using open-circuit spirometry
• Heart rate also monitored
• Test takes 8-16 min

Oxygen Delivery & Utilisation

4 major factors influencing O2 delivery and utilisation to contracting muscle:

1. Respiration

2. Central Circulation

3. Peripheral Circulation

4. Metabolism

1. Respiration

Ventilation

• Not normally a limitation as shown in the last slide of the last lecture – the body normally matches your increased O2 demands by an increase in your VE. Exception: very highly trained where it can’t catch up / disease.
• rate and depth of breathing

Lung Perfusion

• matching of ventilation (air flow) with lung perfusion (blood flow)
• VA/Q

Haemoglobin-Oxygen affinity

Oxygen diffusion

• from alveolar to capillary

2. Central Circulation

Cardiac Output: volume of blood pumped by heart to periphery. Most likely the major factor to VO2 max – how large your heart is and how much O2 it can transport. We usually don’t have enough Q at high work loads to pump to contracting muscles.

Haemoglobin concentration: capacity of blood to carry oxygen

Haemoglobin saturation: amount of oxygen bound to haemoglobin

3. Peripheral Circulation

Blood flow: decrease to splanchnic (organs) area and resting tissues increase to contracting muscle

• capillary density
• arteriolar vasodilation (capillaries open up to allow more blood to flow through them to allow quick transfer of O2 blood to muscles)
• blood pressure

Haemoglobin de-saturation

Oxygen diffusion: from capillary to muscle/mitochondria

4. Metabolism

• Substrate availability
• Skeletal muscle mass
• Muscle fiber energy stores
• Myoglobin content
• Mitochondrial content (oxidative potential) – this is one of the major factors influencing O2 consumption.

Oxygen Delivery & Utilisation

It’s not normally the extraction of O2 and utilisation at the tissue that limits performance, it’s usually the bodies ability to DELIVER  O2 TO THE TISSUE. (But we don’t know this for every individual for certain).

Limitation is mostly viewed as occurring through delivery rather than utilisation:

If something is limiting performance it normally adapts when you train it. One of common adaptations to endurance athletes is they get a larger heart (LVentricle mass) and pumps more blood with more force. i.e. SV.

Whereas maxHR trained and untrained person are quite similar, it’s not really a limiter to performance.

Occurs at level of central and peripheral circulation

• possibly cardiac output (stroke volume)?
• oxygen diffusion from capillary to mitochondria?

Respiratory system generally not seen as limitation:

• PO2 decreases very little
• may be limiting at altitude or in elite endurance athletes at high exercise intensities

Other Factors affecting Maximal Oxygen Uptake *Post

1. Body size: Larger muscle mass increases VO2max

2. Age: VO2max usually declines with age

They say males/females drop about 10% VO2 per decade (1% per year) after age 40~.  The more active you are the more you can buttress this decline.

3. Physiological Differences in Gender: *Post

Males have more Hg than females – thus a higher O2 carrying capacity because we know Hg transports O2 throughout the body.

Males generally/relatively have larger and more muscle mass which practically means they can consume and transport more O2.

• VO2max lower in females compared to males
• Smaller heart size, so smaller stroke volume
• Lower haematocrit (the ratio of the volume of red blood cells to the total volume of blood)

These factors primarily act to decrease oxygen delivery

4. Muscle fibre composition

• Higher proportion of slow twitch-oxidative fibres (Type I) = higher VO2 max potential

5. State of training

Previous cycles of training that influences central/peripheral fatigue

6. Fatigue (effects of prior exercise)

Maximal Oxygen Uptake & Performance

VO2max is one of the biggest determiners to fitness. It generally correlates with exercise performance, but other factors may also influence endurance performance

Percentage % of VO2max

Having a high VO2max is important but what % of VO2max that you can sustain is influenced by lactate threshold and running economy. The % of VO2max that can be sustained is very important.

You could have 2 athletes who have the same VO2 max, and athlete A can sustain their lactate threshold at 90% of their VO2 and athlete B can sustain theirs at 92%, the one you can sustain a higher % difference of lactate threshold will win. VO2 max is important, but what % can you sustain. That’s why you don’t just perform at high % of VO2 max to improve how long you can sustain for, you do shorter duration interval type training at your race pace, slightly above it and below to improve the sustainable intensity.

Predicting performance from VO2max

 

---

Topic 4: Exercise in Extreme Environments

Lecture 19: Thermoregulation & Exercise

Thermoregulation = your bodies ability to maintain it’s core temperature

The Human Cost: Rate of Heat Stroke Fatalities in American Football

Temperature Homeostasis

Temperature homeostasis goal is to maintain constant body core temperature: heat loss must match heat gain

Normal core temperature is 37°C (98.6 °F)

> 45°C may destroy proteins and enzymes and lead to death

< 34°C may cause slowed metabolism and arrhythmias

Homeostatic Temperature Feedback Loop

Heat Production

Voluntary

Exercise

Foodstuff + O2 → Heat + ATP + CO2 + H2O

20-30% stored energy in CHO, fat and protein is “consumed” for ATP production

Whereas 70-80% of energy expenditure “lost” as heat *Post (the term ‘lost’ is clarified in the 4 points below)

The average person would likely assume the majority of stored energy get’s utilised for ATP production (facilitate exercise) but in fact the majority of energy expenditure is through heat production/loss.

Involuntary

Shivering: ~5 fold increase in heat production/energy expenditure *Post

Non-shivering thermogenesis: Mediated by hormones eg. Thyroxine, Catecholamines

Heat Loss

May occur via: Radiation, Conduction, Convection, Evaporation

Heat Loss: 1. Radiation

Radiation is the transfer of heat via infrared rays (the sun)

There are a few different sources of heat loss that can occur:

via the sun, reflective radiation, thermal radiation from the ground heating up,

At rest about 60% of heat loss is due to radiation

It can be a method of heat gain or loss depending on environmental conditions

Heat Loss: 2. Conduction

Where a heat transfer between objects that are directly contacting each other occur

e.g. standing on hot sand at the beach, standing in the water

The method of heat gain or loss depends on temperature difference between objects (e.g. a hot object will want to conduct heat to a cooler object once contact is initiated)

Note: during running not so important as only a small portion of your body comes in contact with ground.

Heat Loss: 3. Convection

A form of conduction

Heat transfer to air or water in contact with the body, where the fluid is moving (e.g. swimming)

The key difference between conduction and convection is whether or not a fluid is moving. E.G. A cool breeze on warm skin is a form of convection, whereas leaning against something cold (brick wall) that’s conduction, standing in still water = conduction, moving in water = convection

Heat loss dependent on temperature and velocity

At the same temperature heat transfer by water is 25 times more efficient than air

Heat Loss: 4. Evaporation

Body heat converted from a water to a gas: a key for heat loss and thermoregulation: accounts for most (80%) of the heat loss during exercise

E.G. Sweating: As sweat evaporates it draws the heat off the skin and the pressure gradient between the air and the skin (and/or lungs – lungs have evaporation to) removes that heat from the body.

Gas pressure gradient between air and skin or respiratory surfaces removes heat from body

Evaporation rate dependent on:

Temperature difference between the body and the air and relative humidity

Why is humidity a poor environment for thermoregulation? Because there’s less of a difference of gas pressure between your skin and the air. Humidity dictates there’s more relative moisture in the air making it much less efficient for sweat to evaporate into gas and pull heat away from the skin. *Post

Convection currents around the body

Amount of exposed skin (clothing that impairs the ability for heat to dissipate through evaporation)

Heat Loss and Exercise

During sub-maximal prolonged exercise in cool environment:

Evaporation: Is the most important major means of heat loss

Convection: Small contribution (*may play bigger role if on a moving bike getting more air flow)

Radiation: Small role in total heat loss

During 45min submaximal prolonged exercise in cool environment

Heat Loss and Exercise INTENSITY

What happens when we look at increasing exercise intensity?

As exercise intensity ↑ there is a linear ↑ in heat production & body temperature.

Core temperature is proportional to active muscle mass

With higher net heat loss we see higher evaporative heat loss and lower convective and radiant heat loss

Red = sum total energy output

Heat Loss and Exercise

As ambient air temperature increases and intensity stays the same:

Total heat production remains constant

Convective and Radiant heat loss: Decreases as you increase the temp of the room

Evaporative heat loss: Increases

Meaning as the ambient air temp heat increases you rely more on evaporation to maintain core temp as opposed to convection/radiation

Remember: 80% of heat loss (particulary in the heat) is due to evaporation

3 Systems That Change During Exercise In Heat

Results in changes in hormonal, physiological and metabolic responses

Hormones: Catecholamines

Showing that if one group (control) exercise in neutral temp conditions (20 C) and the other exercise in heat you can see both groups increase in Adrenalin (a normal expected response during exercise) but the group exercising in the heat produces more Adrenalin.

Febbraoi, Sports Med 2001

1. Cardiovascular

What happens to the CV system during exercise in the heat?

Responds to increase in core temperature > commencement of sweating

Increased evaporative heat loss (again, up to 80% of heat loss due to evaporation), – risk of dehydration as duration continues

Sweating facilitated by increased skin blood flow (heated via core temp) allowing increased heat loss

“Circulatory conflict” (CC)

Competition occurs between the skin and contracting muscle blood flow

Our body wants to maintain a optimal core temp range, in context of exercise in the heat our body has to divert blood flow to the skin to allow evaporation to occur but that come’s at a cost because you’ve diverted the blood away from working muscles. Theoretically this can have performance detriment implications. *Post (running hills in heat)

The CC increases skin blood flow but reduces central blood volume and venous return *why and how it can have performance detriments

To attempt to maintain homeostasis this results in 1. increased heart rate and decreased stroke volume and 2. Increased heart rate may also result from hyperthermia and elevated catecholamines

Diagram: Showing as % dehydration increases HR concurrently increases with it to counter the decreases in SV and increase cardiac output (remembering Q = SV x HR) to support the high O2 demand and sustain blood flow to working muscles. AKA To maintain Q and SV the HR will be higher during exercise in the heat. *Post

3% dehydration is about 2kg of fluid in a 70kg person. (Average rate of sweating during exercise  = 1.5-3L an air depending on environment)

Dehydration in the heat appears to impair performance (cardiac output and mean arterial pressure), specifically around 3% of dehydration.

combination of dehydration and hyperthermia during prolonged exercise in heat

2. Respiratory

Ventilation tends to drift upward during exercise in the heat

Ve increase during exercise in the heat is not due to an increased PCO2 (as shown in the diagram below) but instead elevated core temperature and plasma adrenaline which stimulate respiratory centre

3. Metabolism

What happens to fuel use and metabolism during exercise in the heat?

Increase in carbohydrate oxidation (elevated respiratory exchange ratio (RER))

Exercise in the heat moderately enhances muscle glycogen utilisation and slightly less fat *Post

Jentjens, Roy L. P. G., Anton J. M. Wagenmakers, and Asker E. Jeukendrup. Heat stress increases muscle glycogen use but reduces the oxidation of ingested carbohy- drates during exercise. J Appl Physiol 92: 1562—1572, 2002.

–

During exercising in heat we see an increase in anaerobic glycolysis and an increase in muscle glycogen use reflected by elevated muscle and blood lactate levels

Exercise in the heat causes blood lactate levels to be higher during 64%~ VO2peak exercise at 35 C compared to 20 C. *Post

–

Elevated blood glucose due to ↑ liver glucose output (liver glycogenolysis)

B: HGP = glucose from the liver: during exercise in the heat your liver breaks down glycogen and secretes more glucose into the blood stream which is one of the reasons we see blood glucose levels elevate as shown in A.

MCR: Metabolic Clearance Rate: A measure of the amount of glucose that the muscle is taking up from the blood, under both environments warm and cold the muscle up-takes very similar amounts of glucose.

Effect of Glucose During Exercise In The Heat Compared to Normal Temperatures:

Summary: During exercise in the heat: liver glucose production increases, blood glucose goes up, the muscle uses more glycogen BUT it doesn’t take up any more glucose from the blood (remember we have two forms of CHO that the muscle can draw on: glucose from the blood and it’s stored form of glycogen in the muscle/liver. So the uptake of glucose from the blood doesn’t change it’s the glycogen  in the muscle that’s broken down which is why we see increases in lactate and CHO oxidation. *Post

Exercise Performance

Increased core temperature results in decreased time to fatigue

Fatigue in the heat is usually not due to decreased muscle glycogen or blood glucose availability (as shown below) it’s the fact you reach a ‘critical level’ – fatigue in the heat is related to a critical level of hyperthermia (~40°C core temp) – this is a safety mechanisms because we know  > 45°C core temp may destroy proteins and enzymes and lead to death. So the question is, if you have to exercise in the heat, what are some methods you can do to mitigate and prolong core temperature rising? (besides becoming more CV conditioned under heat conditions – adaptating, some answers below under ‘strategies’) *Post 

Diagram: If you get people to exercise at the same intensity (70% VO2), under different heat conditions, this diagram show’s how long they can exercise for before exhaustion. We can see here being exposes to 40 C conditions (HT) drops time to exhaustion in half compared to the NT (20 C) group – note, both working at the same exact VO2 max intensity. Obviously this demonstrates how much the heat can effect exercise performance in comparison to moderate environmental conditions. It also brings to the light that exercising in the heat is something most people avoid, commercial gyms are air conditioned and people would rather not prufisely sweat outdoors and suffer in the heat. So very few are adapted exercise in the heat. In a similar way people can build up a heat tolerance to a sauna and spend longer duration’s over a period of repeated exposures, the same can be said for exercise under heat. This is called ‘heat acclimatisation’, so no, training in harsh conditions is not ‘all’ mental, physiology plays a role and heat adaptation is a factor to your performance of exercising in heat. There are many adaptions that occur from heat acclimitasion: use info from *How Long Do These Heat Adaptions Take To Build & Last*

So don’t let yourself be dissuaded by this diagram. If you want to train in the heat, understand it’s effects and potential to improve as you continue to expose yourself to the heat stress. Use it as a challenge to yourself to see how you can performance can improve undeer heat. *Post (fill in the diagram with colors in photoshop + next post discuss the mechanisms of how heat training decreases performance)

Exercise Performance

How does hyperthermia cause fatigue theories:

• Mechanism is unknown
• Potentially decreased drive from motor cortex?

Increased muscle temperature may:

• interrupted E-C coupling?
• impaired mitochondrial function?
• enhanced muscle damage?

Impaired cardiovascular function

• dehydration?
• compromised cardiac output and mean arterial pressure?

Strategies to Reduce Hyperthermia

• Pre-exercise cooling
• Heat Acclimatisation
• Fluid ingestion (next lecture)

Strategies to Reduce Hyperthermia

Wegmann SportsMed 2012 42 (7) 545-564. Meta-analysis on pre-exercise cooling methods to reduce hyperthermia. Most of the studies show noticeable cooling improvement to minimise hyperthermia using things like cold water immersion (top, seems to have the most effect) cooling packs, cold drinks, cooling vests and cooled rooms. Some may have shown deterioration due to a excessively cold or long and they’re core temp dropped to much before exercising.

Heat Acclimatisation (Adapting to Heat)

Repeated thermal stress by:

• Passive heating
• Exercise training
• Regular exercise in the heat (best strategy)

Heat Adaptations Include:

• Reduced/slowed body temperature rise during heat exercise
• Reduced heart rate during exercise
• Increased plasma volume by 10-15 occurring within 2-3 days of exercising in hot environments
• Increased sweat rate and earlier onset of sweating: so your more efficient at evaporation which is our main form of heat loss so if we’re more efficient at sweating (i.e. sweating earlier and more) then we can maintain homeostatic core temp for longer and mitigate time to exhaustion in heat
• Lower sweat sodium loss
• Reduced muscle glycogen utilisation
• Enhanced endurance performance *later time to fatigue

• How Long Do These Heat Adaptions Take To Build & Last *Post

Full adaption takes 2~ weeks however some adaptations will occur within 7 days.

Type of exercise to stimulate adaptation: strenuous internal training for 1~ hour every 2-3~ days and/or longer 1.5-2h more lower intensity bouts

After 2 weeks of heat acclimatisation we don’t see any more benefits (although I doubt any longitudinal year/s long studies have been done on consistent heat training so who know’s, there probably is some more chronic adaptations we don’t know about that some people have developed).

Heat adaptations last minimum 1~ week but probably <1 month (Wendt et al. 2007)

Summary of How Long Heat Adaptations Take To Occur

Powers & Howley

Lecture 20: Fluid Balance & Exercise

Body Water

For a 70kg male:

Total body water (TBW): 60% (of that 60% most of it is locked up within the cells in the body)

Consists of:

Intracellular Fluid (ICF): 40%

Extracellular fluid (ECF): 5% Plasma volume (PV)

A key factor to regulating core temperature is linked to PV. The lower PV you’ve got, the reduced blood volume you’ve got in total, to try and keep the body cool.

15% Interstitial fluid (ISF) (locked up between tissues)

Fluid Loss and Exercise

Plasma volume decreases (10-15%) at onset of exercise

Fluid moves into contracting muscle from plasma due to increases in capillary hydrostatic pressure and tissue osmotic pressure (not initially due to dehydration)

As exercise continues, further decrease in fluid loss due to sweating occurs

Hematocrit:

The ratio of RBC to total blood volume. A hematocrit of 42% means hematocrit is taking up 42% of the tube. High hematocrit may occur if your blood doping with a substance like EPO, or if your dehydrated – the reason for that is because if your losing plasma volume due to dehydration the ratio of hematocrit to total blood volume naturally increases (the ratio, not the absolute amount of hematocrit). Additionally, this is one way we can measure dehydration.

 

–

Subjects lost 6% body weight through sweating after being placed in a hot room (remember once you lose about 3% performance begins to be impaired). Diagram: Show’s only a small amount of water is lost from PV, majority from ICF.

Fluid Balance and Exercise

Dehydration before exercise and during exercise affects hormonal, physiological and metabolic variables, such as:

Temperature regulation, Hormonal responses , Cardiovascular responses&  Energy substrate utilisation

Dehydration impairs exercise performance at around 3%, once we get to about 4% dehydration we start to get in the danger zone of hyperthermia and heat stroke.

Fluid Balance BEFORE Exercise

Hormonal and cardiovascular responses

Moderate cycling exercise when dehydrated (■, ~4% body weight) compared to hydrated (□) conditions

*Post: This graph shows what happens to the CV system (specifically Q) during exercise when the person is either hydrated or they’re significantly dehydrated by ~4% BW.

We can see there is a minor difference within 30-40min of exercise, but the differences big much more stark beyond the 1h – 2h+ mark. Practical implication of this highlights the importance of hydration during long steady state~ exercise.

You’ll also notice adrenaline and noradrenaline are quite elevated in a similar manner. This marked elevation in these 2 hormones seem to be associated with impaired .

Running Performance

In hydrated state (normal) or dehydrated by use of diuretic

7% decline in performance when dehydrated

Note: numbers in italics indicate performance times (min)

*Post Another example showing there can be quite a large difference (3min+) in total running time for a 10km run in a dehydrated state compared to hydrated. Moreover, the differences in running velocity are seen pretty much immediately. Practical Implication: There can be big declines in performance if you start exercise dehydrated.

Exercise Performance

Effect of dehydration and re-hydration on muscle power in wrestlers

Exercise consisted of 10 sets of 22 maximal knee extensions with 30 sec rest between each set

*Post: It’s not just CV endurance exercise that is effected, it’s also muscular endurance. this study looked at total work output in 10 sets of 22 knee extensions with 30sec rest between each set. When they dehydrated one group before exercise they observed a 1-1.5 difference in total work output, then they used the same group again in the forthcoming days, put them in a hydrated state and noticed much improved results. (Problem: Most people aren’t doing that high rep range + what’s the effects on muscle power/speed <10 reps – find a study like that).

Summary: Effects of dehydration *if you start exercise in a dehydrated state

Fluid Balance DURING Exercise

Beneficial effects of fluid replacement during exercise on hormonal, physiological and metabolic variables, such as: Temperature regulation Hormonal responses Cardiovascular responses Energy substrate utilisation

Prevention of dehydration improves exercise performance

Physiological responses (core temperature) during exercise regulated by volume of fluid ingested:

Study: There were 4 groups, NF = weren’t allowed to drink any fluid during 2 hours of exercise etc etc I don’t know the exact amounts.

What you can simply see is the more fluid you drink during exercise the smaller the increase in core temperature. So we can safely say the volume of fluid you invest has a big impact on thermoregulation. *Post

Cardiovascular responses during exercise:

In the same study they didn’t just look at core temp they looked at CV responses. NF = maximal impairment in Q, higher HR and lower SV over the course of 2h. There’s pretty much a dose-response relationship, meaning the more fluid you take in the better your performance.*Post

Metabolic (glycogen and lactate) responses during exercise

Fluid replacement that prevents dehydration spares muscle glycogen

If your becoming dehydrated during exercise and not taking in fluid, we know that we get increases in adrenalin which increases our glycogen utilization during exercise.

This study demonstrates this effect showing that if you consume enough fluid to reduce dehydration you use less glycogen.
The higher bar in the left bar graph of the NF trial indicates the person has used more muscle glycogen during exercise when they were dehydrated compared with FR trial that were NOT dehydrated.

The right graph shows us how our body has a varied reliance on the anaerobic glycolitic energy pathway depending on how hydrated we are illustrated by lower blood lactate levels in the FR group. *Post

Exercise performance is influenced by volume of fluid ingested

This is a study where they had the same group perform 2 hrs at 70%VO2, followed by a 90%VO2 to fatigue at the end of the 2h – so a pretty hard test that may have been trying to replicate an endurance race. They did this on 3 occasions, without fluid (NF), with 50% of fluid replacement they needed to stave off dehydration and then 100% fluid to stave of dehydration entirely in the third attempt (F-50%, F-100%). While it’s only SS at the 100% time to fatigue increases dramatically if you’re not dehydrated with the last group performing ~150 min more with full rehydration compared to when they weren’t dehydrated.

Summary: Effects of fluid replacement

Fluids should be ingested during exercise at sufficient rate to minimise dehydration

Need to ingest volume equal to sweat loss.

How much is that?

1. Weigh the athlete/yourself pre and post exercise and see the difference. Then re-ingest fluid to make sure you/they’re prepared for the next bout of exercise.

2. Now you know for your/their next exercise bout how much more approximate fluid ingestion they need DURING their next exercise bout (obviously adjust for varied environmental conditions and other variables). *Post

Complete re-hydration should occur prior to further competition and training

Great example: Patrick Rafter was playing Andre Agassi, in very hot conditions – Pat ended up losing and succumbing to heat stress. They got him into a lab at Melbourne Uni soon after, replicated the same environmental conditions and measured his sweat rates during exercise and found he was sweating around 3L of fluid every hour under those conditions. It was a 3.5h match – he would’ve sweated 10L+, to stave of dehydration in that instance he would’ve had to drink 10L of fluid and he obviously wasn’t because most people couldn’t cope with that amount of fluid ingestion. Also can give example of Rick, 24k burpee’s, rabdo, dehydration, IV drip. *Post

–

Sweat is hypotonic, so water replacement is generally more important than electrolytes

Sodium (Na+) required if exercise is prolonged (more than >1 hour duration)

Ingestion of carbohydrate also recommended during prolonged exercise

Diagram: Exercise (70% VO2) time to fatigue with no fluid, water, and water plus carbohydrate-electrolytes

The fluid your taking in is usually more important than trying to replace electrolytes lost. Adding electrolytes or CHO in a drink can be beneficial though. Study: Show’s you can go almost 40min longer with CHO+E compared to NF exercising at 70% VO2 (time to fatigue). *Post

Fluid Ingestion During Exercise

There’s 3 key sites for fluid ingestion and they’re all effected in different ways by the volume and composition of the fluid your ingesting. Just because you’ve drunk fluid doesn’t mean your automatically rehydrated. E.G. If fluid just sits in the stomach and doesn’t go anywhere it’s off little to no use because it hasn’t been absorbed by the gut (SI) yet.

1. Rate of Ingestion

Palatability: Temperature, Flavour, Sweetness

Access to fluid: 

Voluntary fluid: if you leave fluid intake up to people to drink what/how much they want without saying anything, they found people will only take in about half of what they lose. *Post

Ingestion of fluids at high rates of 1-2 liter  per hour may be difficult and impractical

2. Rate of Gastric Emptying

Dependent on:

1. Volume ingested

2. Carbohydrate concentration

3. Osmolality (amount of NA+ in a drink): Likely to have only minimal effects on gastric emptying. At the site of the stomach the amount of NA+ in a drink doesn’t have an effect on gastric empting. It’s volume and CHO that are the biggest influences.

Graph: Show’s the relationship of how quickly the stomach empties fluid and the volume of fluid that’s consumed. We can see that up to 600-800ml is where the quickest gastric emptying occurs because the larger volume of fluid puts more of a stretch on the stomach and stimulates it to release into the gut. But there doesn’t seem to be a difference in the rate of gastric emptying between 600ml and 800ml indicating the possibility that that amount of fluid within 15min is the max fluid volume we can empty. Then again who knows what they body can do with something 2L of ingestion in 15min.

Graph: They get a group of people to drink, wait and then get a tube to down to suck out the remainder to work out gastric emptying. Gastric residue show’s how much fluid is left in the stomach. We can see that if you change the amount of glucose in the drink there’s a lot more left in the stomach past the 100mM mark – pretty much the effective of, if there’s more glucose in the drink there’s more glucose in the stomach.

3. Rate of Intestinal Absorption

Water absorption occurs via osmosis, but also linked to absorption of glucose and electrolytes

For effective hydration fluids should contain some carbohydrate and electrolytes

Diagram: When fluid enters the intestine it will diffuse across the lumen (left to right).

Lambert, G. p., R. T. Chang, T. Xia, R. W. Summers, and C. V. Gisolfi. Absorption from different intestinal seg- ments during exercise. J. Appl. Physiol. 83(1): 204—212. 1997.—This stud evaluated testinal absor tion from the

Diagram: Show’s how quickly fluid is absorbed across the intestine. You can see a clear difference in the rate of absorption by putting CHO-E in the drink compared to water alone. Basically showing a little CHO-E in fluid ingestion can speed up intestinal absorption compared to water only. But there’s a limit…next slide.

–

Excess concentrated carbohydrate solutions may impair absorption resulting in fluid (water) secretion into gut lumen rather than absorption into blood

Too much CHO in fluid may impair absorption so what we see is rather than the fluid go from the intestine to the blood, we see fluid from the blood stream secreted back into the SI which is going to cause gastric distress like diarrhoea.

Diagram: Show’s the amount of water absorbed into the blood is highest for an isotonic glucose electrolyte drink, there’s still some absorption going on with just water, then if we have a really hypertonic glucose solution with lots of glucose the water starts causing distress and being secreted through diarrhoea (but is that what ‘water secretion’ implies?)

Isotonic: A solution having the same osmotic pressure as some other solution, especially one in a cell or a body fluid.

Hypertonic:  In this case, the water has more of a solute than the cell does. In this case, water rushes out of the cell in order to maintain equilibrium 

Fluid Ingestion DURING Exercise

In summary: Quantity of fluid ingested during exercise is dependent on sweat rate, but usually ingestion of isotonic solution containing these 3 is optimal:

• electrolytes
• 4-8% carbohydrate (because anymore will impair gastric emptying and intestinal absorption)
• at a rate of 600-1200 ml per hour is optimal for both fluid and carbohydrate delivery

Fluid Ingestion AFTER Exercise

Hormonal responses after exercise (recovery)

There’s a number of anti-diuretic (fluid absorption) hormones that are released after exercise to aid in reabsorbing more water. They promote water and sodium retention by preventing the kidney from passing too much fluid out in urine. As shown in the graph they’re elevated for quite some time post exercise.

• Renin
• Aldosterone
• Anti-diuretic hormone (ADH or vasopressin)

Restoration of fluid balance (re-hydration) following exercise is dependent on:

Ingested volume:

How much fluid should you ingest post exercise? Should usually be greater than sweat loss. Often recommended 150% of the sweat you’ve lost during exercise.

Sodium content: ~50 mmol/l facilitates fluid restoration

–

Whole body re-hydration (% body weight) measured 3 hours following exercise with variable fluid volume and sodium content

This study looked at various amounts of fluid volume and sodium amounts 3h post exercise.

They found high volume fluid re-hydration has a bigger effect on the amount of fluid absorption/retention and sodium has a very small marginal added positive effect to total % re-hydration. However the following diagram will show how NA+ has bigger effects.

–

Plasma volume changes measured 3 hours following exercise with variable fluid volume and sodium content

The same study looking at variable fluid and plasma volume. This group lost 7.5% of their plasma volume during exercise. High NA+ under both low and high fluid volume conditions resulted in well above elevated plasma volume above resting levels compared to lower NA+ ingestion regardless of fluid volume which results in just above resting levels. So NA+ seems to have a positive influence of plasma volume levels.

–

Re-hydration measured 6 hours following exercise with fixed fluid volume (150%) and variable sodium content

Diagram: Dehydrate people, give them 3 fluids with various NA+ concentrations at 150% volume of what they lost, over 6 hours.

The result was the ‘% of recovery of fluid balance’ improved with a higher NA+ concentration up to about 50mM. Going over 50mM didn’t seem to have any more extra benefit.

Practical Implication: NA+ up to 50mM can help you rehydrate more efficiently.

---

Exam Prep

5 short answer questions (1Q from each online topic: muscle/metabolism/O2 transport (cardiopulmonary)/exercise in extreme environments

+ 1Q related to the prac labs: review answers to group prac reports – the question will be a variation of those

Questions based on key learning concepts

---

Extra Notes

Cardiovascular System:

From bouts of rest (lying down/sitting) to standing (e.g. the moment you may get light headed for a moment), gravity results in blood pooling in the inferior portion of the body.

= less blood returning to the heart = decreased arterial pressure sensed by baroreceptors >  decreased firing > relayed to medulla oblongata > stimulation of sympathetic NS  AND > inhibition of parasympathetic NS (which is why HR increases rapidly after standing up from sitting)

These are acute responses that occur for 30-60sec to help restore the body to homeostasis.

Feet up against the wall supine lying down: helps venous return. This position can greatly help blood flow back forward/backwards through the rest of the body, especially for the extremities which rely on pumps/valves to pump blood back to the heart against gravity when standing. Now we’re using gravity to our advantage.

Dynamic Exercise: Blood vessels dilating more and more as exercise continues to account for more blood volume being distributed from the heart to the rest of the body – so BP may either maintain or not change significantly due to capillary dilation.

Effectors of Blood Pressure Control

The Heart

Sympathetic (Cardiac Nerves)

–Release of nor-adrenaline which innervate SA (sino atrial node), atria and ventricles

–Causes an increase in both heart rate & contractility

Parasympathetic (Vagus Nerve)

–Vagal stimulation decreases heart rate by its effect on the pacemaker activity (SA Node)

–Muscarinic receptors are stimulated by Ach and inhibit the SA node pacemaker cells to reduce heart rate

Blood Vessels

Sympathetic

–Sympathetic influence on blood vessels causes vasoconstriction

Except in skeletal muscles it causes vasodilation

–Sympathetic vasoconstrictor fibers are located throughout the body & release nor-adrenaline

–Nor-adrenaline stimulates alpha-1 receptors causing vascular smooth muscles to contract, resulting in vascular constriction

Parasympathetic

–Parasympathetic fibers causes vasodilation, but are far less common than sympathetic

–They are mainly concentrated in salivary & some GIT glands, plus the external genitalia

–Elicit their effect by release of ACh and NO