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The Physiology Behind it All
    In this section you will find out several things including what is going on in your body during training, what you are trying to accomplish to run faster, what limits performance in certain events, and what workouts can be done to improve these factors.

  1. Increasing_the Oxygen_supply_to_the muscles
    1. Increase_in_oxygen_Delivery_to_the muscles
      1. The_amount_of_Air_that_can_be_taken_in and diffused to bloodstream
      2. Increase_in_Hemoglobin
      3. Increase_in_Blood_Flow:
        1. By_an_Increase_in_Blood_Volume
        2. By_an_Increase_in_muscle_Capillaries
        3. By Improved_blood_redistribution
      4. Increase_in_Ventricle_size_and_thickness
      5. Increase_in_Myoglobin:
    2. Increase in Oxygen_Utilization_by_Muscle
      1. Increase_in_size_and_number_of Mitochondria
      2. Increase_in_Aerobic_Enzymes
  2. Improving_how_your_muscles_deal_with Lactate
    1. Improving_Lactate_Removal
      1. Training lactate removal
    2. Improving_Buffering_Capacity
  3. Muscle pH and Acidosis
  4. Increasing_Muscle_Glycogen_stores_and Glycogen Storage
  5. Lactate_Transporters
  6. Causes_of_Fatigue
    1. Metabolic_Fatigue_Theory
      1. Central_Fatigue


1.  Increasing Oxygen supply to the muscles (Increasing VO2max)

    Increasing VO2max (maximum oxygen consumption or uptake) is an important aspect of training.  To see specific details on this read The Basics section in the Training page.  Basically the more oxygen that can be delivered and used by the muscles, decreases the accumulation of hydrogen ions in your muscles, so that the muscles can work longer at the same intensity before the muscle fibers fail, or the intensity can be increased to a new level over the same original time period.   Thus to improve this, we have to look at two different aspects that might improve oxygen consumption.  They are an increase in the delivery of the oxygen to the muscles and an increase in the amount of oxygen that can be used by the muscles.
      

Increase in oxygen Delivery to the muscles
    The amount of oxygen delivered to the muscles depends on several things.  The first is how much we take in and gets into our blood stream.  The second is how much of that oxygen that we take in can be transported through our blood stream to the muscles that need it.  Below are the aspects that regulate these two factors.  Some of them are a limit to performance and can be improved while others don't limit performance and do a more than adequate job and even if we could improve them, it wouldn't make much of a difference.
  1.     The amount of Air that can be taken into bodies each minute through respiration and the amount that diffuses into the blood stream: The primary limiter in this is the amount of Oxygen that diffuses from the lungs into the blood stream through the aveoli and capillaries.  We have more than enough aveoli to get the job done, but pullmonary capillaries can be increased.  However even with this increase, it doesn't appear that this diffusion between the lungs and blood limits performance.  This is because more oxygen is present in the aveoli than can be taken up and carried to the muscles by the Hemoglobin.  In other words there's not enough Hemoglobin to transport all of the oxygen that's already in the aveoli.  The amount of air that can be taken in does respond to change, but most agree that any exercise that increases breathing will bring the athlete to max rate in the amount of air that can be taken in shortly.  Plus as I said earlier, it doesn't seem to be the amount of air that can be taken in that limits the amount of oxygen that gets to the muscles, it's the Hemoglobin that carries it.
  2. Increase in Hemoglobin: Since the amount of Hemoglobin in the blood seems to limit the amount of oxygen that can get to the muscles, then increasing the amount of Hemoglobin sounds like a good idea.  Increasing the amount of Hemoglobin would increase the amount of oxygen that could be taken from the aveoli and carried to the muscles.  Unfortunately, increasing Hemoglobin seems like it's hard to do.  Altitude training has been shown to increase Hemoglobin levels by as much as 7%-18% (Karvonen, 1986; Green, 1991) but has also been not effective and provided no increase to some individuals.  This is where you get the idea that there are altitude responders and non-responders.  Besides altitude training, the other effective ways are blood doping and taking EPO, both of which are illegal and very dangerous.
  3. Increase in Blood Flow: Increased blood flow allows for more oxygen to be delivered to the muscles.
    1. By an Increase in Blood Volume: While an increase in hemoglobin is a good thing because more oxygen can be carried to the muscles, the increase tends to thicken the blood therefore reducing how fast the blood moves throughout the body.  Thankfully your body counteracts this increase in thickness of the blood by increasing the total blood volume.  This increase in blood volume makes the blood more fluid so that it can flow faster.  This increase in blood volume seems to occur best at more intense training levels. This is just one way of the ways that increased blood flow occurs.
    2. By an Increase in muscle Capillaries: An increase in muscle capillaries will allow for more oxygen to diffuse through the capillaries and into the muscles to be used.  There have been many studies conducted that show that it is possible to increase muscle capillaries by between 15-50%.  Because an increase in capillaries is a muscular change, only those muscle fibers recruited will be forced to adapt and increase the amount of capillaries.  For this reason, adaptations only take place in those fibers recruited.  This is where the principle of specificity comes in.  Running recruits different fibers than other sports such as cycling.  If you cycled a lot, then you will improve several aspects of fitness, but muscular changes such as increased capillaries or mitochondria won't take place in the same muscle fibers as in running.
    3. Improved blood redistribution (Blood Shunting): This process refers to how effective your body is in directing blood to the muscles that need it.  Your body redirects blood to the muscles that are being used during exercise.  It can get better at this process by directing a greater percentage of blood to the working muscles through training.  This happens because your body becomes more efficient at this process and certain blood vessels dilate or constrict based on whether the muscle needs or doesn't need the blood flow.  Aerobic training is the best way to improve this, but it's not known whether it's high end aerobic training or not.  This is another muscular adaptation, so it falls under the principle of specificity.
  4. Increase in Ventricle size and thickness: Increasing Stroke Volume (the amount of blood ejected with each heart beat) increases the maximal cardiac output (the amount of blood that is pumped per minute).  In order to increase the stroke voume sufficient stress has to be put on the heart to induce adaptations to it so that it can pump more blood per beat.  Some of these adaptations include an increase in the Left Ventricle wall thickness, increase in LV size, and a more complete emptying of the ventricle.  There is debate in how to accomplish these changes.  In Martin and Coe's Better Training for Distance Runners an increase in LV wall thickness was found with strength-oriented training, while an increase in LV size and a more complete emptying was found in Endurance oriented training.
  5. Increase in Myoglobin: An increase in Myoglobin will increase VO2max by enhancing oxygen movement from the Sarcolema to the mitochondria¹.  There has been some debate to whether or not training can increase this aspect.   So far studies have found that in rats myoglobin concentration has been increased when trained at intense speeds that were probably around 100% VO2max².  In humans studies that have tested athletes at relatively low to moderate intensities (below LT) no increase in myoglobin has been seen.  However studies involving training in hypoxic environments have been shown to increase concentration.  So what does all of this mean?  Well it MAY be possible to increase myoglobin stores in normal training conditions but it will most likely require intense speeds of 100% VO2max or greater.
(1.Wittenberg JB, Wittenberg BA. Myoglobin function reassessed. J Exp Biol 2003; 206: 2011-20
 2.Hickson RC. Skeletal muscle cytochrome c and myoglobin, endurance, and frequency of training. J Appl Physiol 1981)
Increase Oxygen Utilization by the Muscles
    So far I've only mentioned changes that can improve the delivery of oxygen to the muscle through the bloodstream.  Now we'll look at certain aspects that can be changed to increase the use of oxygen by the muscle once it has been delivered.
  1. Increase in size and number of Mitochondria: In the training section I briefly explained what these were and why they are vital to your running.  As a refresher they are the "aerobic powerhouse" where aerobic breakdown occurs.  Thus if you have more aerobic metabolism can take place more often and quicker.  Because of this, the rate of lactate production decreases.  Since this a muscular change, the principle of specificity applies.  Only those muscles used during the exercise will get the adaptations.  So cross training isn't as effective as actual running if you want to work on an increase in mitochondria.  Since an increase is also specific to what muscle fibers are recruited it only makes sence that in training for this change, slow to medium runs will benefit ST fiber mitochondria, Lactate Threshold speed and up to 100%VO2max speed will recruit the FT-A fibers, and speeds of 100%VO2max (about 3k speed) and faster are needed to get adaptations in the FT-B fibers.  So as you can see, a variety of paces are needed to stimulate mitochondria increase in all muscle fibers. It should be noted that Long Runs have been shown to deplete the ST fibers so that some FT fibers will cycle in and be used.  So Long runs can be used to increase mitochondria in some FT fibers.  While a variety of paces does need to be used, too much faster paced running above the Lactate Threshold can actually damage mitochondria.  Some studies have shown that after high acidosis training sessions, mitochondria have been damaged beyond repair.  High acidosis training includes hard sessions that lower the pH of the muscle.  These are intense sessions that are above the Lactate Threshold.  In my training session, both VO2max and anaerobic work such as Lactate Tolerance work can be considered high acidosis training.  That's why this type of training should be used only so often and plenty of rest given afterwords for tissue repair.  One other danger of training to mitochondria is when training with low glycogen stores.  When your muscle glycogen supply is low, your body has to rely on other sources more and more for energy such as Fat and protein.  THe problem is that protein isn't stored in your body like fats and carbohydrates.  The protein in your body are the various enzymes, organelles, and structures such as mitochondria.  So if you are severely glycogen depleted then your body might breakdown proteins like mitochondria for energy.  That's why it's not advised to do a hard workout after a long run or long threshold workout because glycogen stores would be low.
  2. Increase in Aerobic Enzymes: An increase in Aerobic enzymes allows for aerobic breakdown to occur faster because there are more enzymes available for the reaction to take place.  Aerobic enzymes are substances that are used during chemical reactions during Aerobic metabolism.  Many of these enzymes catalyze (transform or increase) reactions.  An example of this is when the enzyme acetyl-CoA synthase helps to connect the seperate substances of Acetyl and Coenzyme A.  Increasing Aerobic enzymes are a muscular adaptation, like mitochondria or capillarie increases, so they fall into the principle of specifity.  To refresh, this means that only those muscle fibers used will adapt.  Therefore, it's important to use a mix of intensities in order to get adaptations in all of the muscle fiber types.  According to some studies (Henriksson 1992 cited in Maglischo 2003) the largest increase in aerobic enzymes occurs when training at an intensity that is near the Lactate Threshold.  This makes sense because at this intensity the athlete is using both ST and FT-A fibers.  But if this is true, why would a faster intensity of 100%VO2max or greater not increase aerobic enzymes more since that intensity would recruit ST, FT-A, and FT-B fibers?  This is because of the corresponding acidosis that occurs at such intensities.  Aerobic enzyme activity decreases as muscle pH decreases.  This explains why a pace at the LT shows the greatest increase.  It's simply because this is the fastest pace that one can run without an accumulation of lactate and the corresponding hydrogen ions that correspond with a lowering of the muscle pH.  One more positive aspect about increasing aerobic enzyme activity is that it seems to occur in even very highly trained athletes who have reached a steady VO2max.  This means that it can most likely be improve even after an athletes been training at a high level for a long period of time and has relatively maxed out his VO2max.
Improving how your muscles deal with lactate build up:
    Lactate build up in the muscles has been shown to correspond with hyrdogen ion build up and a drop in the muscle pH.  While lactate itself does not impair performance or cause the muscle fibers to fail, it corresponds greatly with the build up of substances that we think cause fatigue and muscle fiber contraction failure.  Lactate is easier to measure than these other substances, so that is why you will commonly hear training terms such as delaying, buffering, or removing lactate.  The thought is that if you can remove or buffer lactate, then the corresponding elements that cause fatigue will be removed too.  That's why lactate is still commonly used in scientific and training literature as something that needs to be gotten rid of or buffered.  For this reason, the following discussion will focus on how to train the muscles and body to remove lactate, improve the buffering capacity, and improve tolerance to lactate.
  1. Improving Lactate Removal: If lactate couldn't be removed from the muscle, then it would just sit there and accumulate and that muscle fiber would eventually stop contracting because the muscle pH would be lowered by so much.  To help alleviate this problem and allow the muscle to work longer, the body allows for the removal of lactate from the muscle through several different methods.  Lactate can be taken up by the muscle in which it was formed and converted back into pyruvate and then used for aerobic energy.  If the muscle cannot convert the lactate back into pyruvate, then the lactate will move from an area of high concentration to one of low concentration.  Because of this it will enter part of the lactate shuttle and be transported to the area between muscles, the interstitial fluids.  From their, the lactate can either be transported to an adjacent muscle fiber than can take up the lactate and use it for energy or it can enter the blood stream.  Once in the blood stream it can be transported to various parts of the body.  Another muscle that hasn't reached it's max capacity for taking up lactate and using pyruvate for energy can take up the lactate from the bloodstream and use it for energy.  This often occurs in muscles that aren't used or are used less during an exercise.  For example in running, a muscle in the leg may be overloaded with too much lactate and transport it to the blood stream and then from their up to a muscle in the upper body which isn't being used to it's full capacity.  Lactate in the blood can also be used by the heart as an energy sourse or be sent to the liver and coverted to glycogen.  This lactate shuttle that takes lactate to other muscles, the liver, or the heart allows for the difference in lactate concentration between the muscle and blood stream to remain higher than if lactate couldn't be taken up by these other sources.  Because the difference remains somewhat higher, than more lactate can flow out of the muscles and into the blood instead of accumulating in the muscle and causing fatigue.  Even when the difference in concentration is not at max, lactate transporters help to push lactate out of the muscle.
    1. Training: Lactate removal can be trained by enhancing the aerobic system of the muscles.  With more aerobic adaptations (mitochondria, aerobic enzymes, capillaries, etc.) more of the lactate can be converted to pyruvate and used as energy in the aerobic system.  The training for lactate removal depends on several things, two of which are the ability of muscles which aren't producing excess lactate to use the lactate in the blood stream, and the ability of your cardiovascular system to shuttle lactate to various parts of the body that can use them.  Also, an increase in lactate transporters will allow for muscle fibers to transport more lactate out of the muscle.  To improve several of the factors that affect lactate removal the specificity principle applies.  This means that only those fibers used will adapt.  For this reason, a variety of intensities is probably needed to work on the ST, FT-A, and FT-B fibers.  Most of the training for this purpose should probably be easy/steady running up to Lactate Threshold speed.  Although some studies have suggested that the max rate of lactate removal occurs when blood lactate levels are just above lactate threshold levels.  Training speeds of 100% VO2max or better are needed for training the FT-B fibers, but these should be done in moderation, as some studies have shown that lactate transporters are less effective as the muscle pH drops (Roth and Brooks 1990 cited in Maglischo 2003).
  2. Improving Buffering Capacity: Our muscles and bodies can not eliminate or clear out  lactate in our muscles at near the rate of it being produced or accumulating even if your lactate removal system is trained to it's max genetic potential.  The rate of lactate production in middle distance races far exceeds the max rate of lactate removal.  Therefore, an accumulation of lactate is inevitable in the muscles.  This accumulation will eventually bring on fatigue and cause the athlete to slow and tire during a race.  However, our body has specific substances in the body which weaken the effect that hydrogen ion accumulation has on muscle pH.  These substances help to slow down the muscle pH drop and are called buffers.  These buffers are present in both the blood and muscle and include the alkaline reserve (bicarbonates), creatine phosphate, and other proteins.  The most effective method to improve buffering capacity seems to be training that has an effect of moderate to high level acidosis.  This acidosis is probably required to stimulate the need for a greater number and improved buffers.  Just like in most things, too much can be a bad thing.  Too much high acidosis training will destroy some buffers.  In addition to this heavy aerobic training (threshold and easy or long distance runs) may suppress the buffering capacity.  That's why there needs to be some sort of balance and an extended period of just distance running will lower your buffering capacity too low that it can't be brought up.  It needs to be maintained somewhat during a base training phase.  It should be expected that the buffering capacity will fall somewhat, but only to a level where it can be elevated back to normal levels or higher rather quickly.  The reason for a period of heavy anaerobic training before a peak racing period is to bring the buffering capacity back up after a base period has been done which probably suppressed it.
Muscle pH and Acidosis
       A major contributer to fatigue in middle and distance races is a drop in muscle pH and the onset of acidosis.  Acidosis occurs when hydrogen ions accumulate in the muscles.  These Hydrogen ions are formed during anaerobic metabolism.  As they accumulate in the muscles the muscle pH begines to drop too (the muscle becomes more acidic.)  Lactate accumulates in the muscle in the same proportion as hydrogen ions, even if one does not directly cause the other.  Because of this 1 to 1 relationship, it is one reason why scientists and athletes use lactate measurements.  Hydrogen ions also leave the muscle if the corresponding lactate leaves.  That is why one of the goals of training is to increase lactate removal from the muscle (see above section).
       A drop in muscle pH causes a decrease in speed for several reasons.  One reason is that the increasing acidity seems to cause the burning sensation felt in the legs.  This acidity in the intracellular fluids of the muscle stimulate pain receptors.  Depending on the pain tolerance of an athlete, this pain can cause an athlete to slow down at some point.  This pain may also be a defense mechanism of the body telling it that it cannot continue at the current speed for much longer.  The second reason is that once the muscle pH drops below about 7.0 (from the normal 7.2-7.4) then the rate of ATP recycling diminishes.  In fact when the muscle pH reaches 6.4, Anaerobic metabolism can not take place (Maglischo 2003).  The reason for this is that the lower the pH gets the more calcium is required for muscle contraction.  Calcium is essential in muscle contraction.  In addition to this the more acidic the environment, the less activity of particular enzymes there is.  In regards to Anaerobic metabolism, the enzyme ATPase activity is decreased as muscle pH drops.  With this decreased activity that means that the breakdown using these enzymes must be slower, since there are not as many active to "help out."  Besides these two reasons, a substance that regulates anaerobic metabolism, PFK (
Phosphofructokinase
), is reduced which in turn slows anaerobic metabolism.

Increasing Muscle Glycogen stores and sparing glycogen
       The amount of training we can do from day to day depends on several things such as how fast our muscles repair or how fast our glycogen stores are replenished.  In this section I will focus on the latter.  Glycogen is the primary and preferred fuel used in running.  It provides evergy with much less steps and quicker than the other two sources (proteins and fats).  In addition it can be used with or without oxygen present.
    When our glycogen levels are low it limits our ability to train.  Our bodies have to start switching to another energy source which is less efficient.  This means we can not keep up the same speed or same effort.  Also, in cases in which protein is used as a source this can be detrimental too several key structures in our muscles.  Several of the structures in our muscles (mitochondria, enymes, etc.) are made up of protein.  Protein is not stored for energy use like fats or carbohydrates (glycogen).  Because of this, when protein is used as a fuel source, it must come from these and other like structures that are made up of protein.  This means when you are using protein as a fuel source, you might be damaging the structures in the muscles that you spent so long to build up!
        Because of this, it's important to only rarely train with low glycogen stores.  Thus one of the adaptations that will allow you to train more is an increase store in glycogen or a sparing or saving of glycogen at lower intensities.  Endurance training has shown to increase muscle glycogen stores.  However, athletes who train 2 or so hours a day probably are not replenishing there glycogen stores completely.  Thus they never realize that their maximum storage capacity is increasing.  Glycogen stores are not fully restored until a couple of light days have been taken or after rest.  This is similar to what happens during a marathon runners carbo loading and taper session.  He is trying to maximize the increase of his storage capacity before the marathon.  It is also important to note that an increased storage of muscle glycogen only occurs in the muscles that are being used.  So it is a specific adaptation.
       If this adaptation can only be realized after down days, how can it help you train more or better?  What happens is that you increase the max storage available.  So if you start out at let's say 200g stored and then train it will take you longer to deplete it if someone starts out at 150g and trains the same way.  Let's say that for 4 days both athletes do the same run that depletes their storage by 50g.  During the rest periods, they replenish 20g of that.  The following chart illustrates the phenomenon.
(this is not typical glycogen depletion/replenishment, it's just done to show a simplified idea of why it's important to increase glycogen stores for daily training.)

200g Max person
150g Max Person
Day 1-before run
200
150
Day 1-after run 150
100
Day 2-before run 170
120
Day 2-after run 120
70
Day 3-before run 140
90
Day 3-after run 90
40
Day 4-before run
110
60
Day 4-after run 60
10
Day 5-before run 80
30
Day 5-after run 30
0- stops run before end
Day 6-before run 50

Day 6- after run
0

       As can be seen in this simplified version, the person with the higher max can run at the same intensity for another 1.5 days compared to the person who had the lower max.  This means he can train at that intensity longer before he needs rest or low intensity running to allow for his glycogen stores to increase back to normal levels.  Of course training does not occur like this in real life and the amount of glycogen used and restored will vary based on numerous factors.  This simple chart can show why endurance training is important to increase glycogen stores not only for races that are limited by glycogen supply but also for training purposes.  That is one reason why endurance training and long runs can be beneficial for those who are running as little as a couple of minutes.  It allows them to train more and better without breaking down because of glycogen depletion.  One last thing to cover on glycogen storage is that I said that most runners never reach their max until a few light days or off days.  Does this mean it is pointless to increase the max if you rarely reach it?  No, because think about at the begining of the season when you have taken time off and trained sparinlgy.  You probably have near max stores at that point.  Also when you take a down week or a day off or even several light days in a row to allow for recovery during the season your probably restoring close to your max.
       One other thing that is important is sparing glycogen during running.  At low intensities your body will use fat as fuel.  This can be accomplished because their is plenty of oxygen available and the intensity is not so great that their is not time to go through the lengthy process of converting fat to fuel.  As the intensity increases, using fat as fuel becomes less and less because it takes to long.  So on easy to moderate runs it would make sense to teach the body how to get away with using as much fat as possible when the intensity is low enough that it won't affect your pace in order to save the glycogen for when it is needed.  Endurance training has been shown to increase the amount of energy that is derived from fat at low to moderate intensities.  This occurs partly because of an increase in mitochondria and in the enzymes responsible for fat metabolism.  The best way to increase the amount of fat metabolism at these intensities is by long slow to moderate paced running.  This is just one mor ereason for easy running and long runs for even short events.  It will promote more fat metabolism at easy to moderate intensities so that less of that energy comes from glycogen.  Thus on your easy to medium days, less glycogen will be depleted, meaning more time to train.

Lactate Transporters
       When lactate is produced in the muscle it can either accumulate in the muscle or be transported out of the muscle.  When it is transported out of the muscle, it can be transported to neighboring muscles, move to spaces between the muscle, or be transported into the blood stream and then delivered to various other tissues, including other muscles or the liver.  In order to be transported, lactate transveres the sarcolemma  using a transport system.  This system uses various porteins to help transport lactate out of the muscles.  It's important to note that lactate ions and Hydrogen ions are cotransported, meaning that they are transported out of the muscle together.  This is important because a build up of hyrdogen ions lowers the muscle pH, causing the muscle to be more acidic.  When this happens, the muscle does not function as well.  For example, certain aerobic enzymes do not work in a highly acidic environment.
        Currently 14 different lactate transport proteins have been found.  These are called monocarboxylate transporters (MCT) and are numbered 1 through 14.  The discovery of these is relativelyt new so therefore there is a lot that is not understood about the MCTs.   The two most studied and understood ones are MCT1 and MCT4.
       MCT1 has a moderate affinity to lactate.  It has been shown that the amount of MCT1 in the muscle is directly related to the aerobic capabilities of that muscle.  In addition to this, MCT1 concentration is tied to the number of ST fibers and FT-A fibers.  The more oxidative the fiber, the higher the MCT1 concentration.  Also, the more MCT1's, the more lactate uptake.  With all of this information, the role of MCT1 is beliueved to be one of fascilitating the uptake of lactate from the blood stream or from neighboring muscle cells. 
       MCT4 has a very high affinty to lactate and in humans these are only found in the Fast Twitch fibers.
  MCT4 shows the exact opposite relation to lactate uptake as MCT1, the more MCT4's, the less lactate uptake.  MCT4's role is believed to be one of transporting the lactate out of the muscles.
       Now kowing that MCT1 is involved in taking up lactate and that MCT4 is involved in transporting it out of the muscles, what does this mean in regards to running performance?  If you can increase the amount of these two transport proteins, then lactate can be transported out (via MCT4s) faster and can be taken up by muscles that are not heavily used in running (via MCT1s).  Lactate transport out of the muscles is important because you want to be able to get the lactate and the associated hydrogen ions out of the muscle to limit the acidity of the muscle.  This allows muscles to work longer before reaching high levels of acidity.  Lactate uptake by muscles is important because it can take the lactate out of the blood stream and allow it to be oxidized by muscles that aren't heavily involved in running.  By taking the lactate out of the blood, this allows for more of that lactate to be transported from the hard working muscles to the blood because lactate move from levels of high concentration to lower concentration areas in general (From muscle to blood, then blood to non lactate producing muscles that aren't being taxed during running.)

(sources: Physiology of Sport and Exercise by Costill and Whilmore, Better Training for Distance Runners by Martin and Coe, Swimming Fastest by Ernest Maglischo, Secrets of Lactate CD-rom)

Causes of Fatigue
    The name of the game in training a runner boils down to delaying the onset of fatigue and then teaching the body how to deal with it better.  It sounds simple enough, but what exactly causes fatigue?  What is it that causes a runner to tire and hit the wall during the marathon or tie up at the end of a hard mile?  The answer to these questions is a complex one and admittedly we do not know all of the answers.  There are several theories in regards to what causes fatigue, some more accepted than others.  In the following section, I will do my best to describe the most accepted theory and then some of the more well known but controversial theories.
 
Metabolic Fatigue Theory
       Before beginning it is important to define what fatigue actually is.  It is easy to see in the real world but for scientific purposes fatigue can be defined as "failure to maintain the required or expected power output" (source:Exercise Metabolism).  Keep this definition in mind as we look at the various components of fatigue.
       Central Fatigue- Central fatigue can be defined as a decline in power when comparing a voluntary exercise or contraction as compared to a stimulated contraction.  What this means is that if the muscle/person fatigues faster than when the muscle is stimulated, then an element of central fatigue is playing a role.  The Central Nervous system plays a key role in this type of fatigue.
       In order to recruit the muscle fibers to contract a certain threshold of stimulation is required to activate those fibers.  Slow Twitch fibers have the lowest activation threshold meaning that it takes a relatively small signal to activate and contract these fibers.  As you progress down the muscle fiber spectrum to Fast Twitch fibers the activation threshold becomes larger, meaning that a larger signal needs to be sent to activate them.  In order to recruit these higher threshold fibers, a large neural drive is needed which means high motivation.  This is where the Motor Cortex comes in.  It is a part of the brain that controls and guides movement in the body.  It does this by sending a signal from your brain down through your spinal cord and to the muscle that requires action.  Several things may impair this process somewhat and thus lead to "fatigue."
       This is where pain or discomfort comes in.  As the exercise becomes more painful the neural drive and motivation diminishes, thus the signal strength sent to the muscles does not meet the required threshold for activation of those muscles.  Thus, this is one mechanism to explain why muscles "fail."  There are several aspects that may cause this pain and the reduced drive.  Studies have shown that an elevated core temperature seems to coincide with this and may impair exercise at the motor cortex level (1).  Another thing that might contribute to central fatigue is Dyspnea, which is just a fancy word for difficult or labored breathing.  This labored breathing is related to lactic acid accumulation in the blood, and thus an increase in Hydrogen Ions.  So this increase in H+ might indirectly cause central fatigue.
        There are several metabolic changes that take place that could also contribute to an impairment at the Motor Cortex level.  The first of those is having low levels of blood glucose (hypoglycemia).  This is important because blood glucose is the main source of fuel for the brain and thus impair the CNS.  Low blood glucose occurs when one is glycogen depleted, particularly their liver glycogen stores.  This happens during long runs or races if some form of Carb isn't taken in (i.e. the marathon).  Another aspect to consider is the increase of ammonia that occurs during intense or long exercise (2).  There is less of a case made that it directly causes fatigue, but theoretically it could since ammonia is a neurotoxin.  Another thing to consider is a decrease in plasma levels of Branched Chained Amino Acids (BCAAs) that occurs during long endurance exercise.  This drop in BCAAs and an increase in tryptophan may contribute to central fatigue because these two things compete against one another for transport into the brain (3).


Possible Contributions to Fatigue in different races (updated as I add more sections):
Long races (2hr plus)
-Central Fatigue to Motor Cortex via...
    - low blood glucose levels.  The CNS can not function as well with reduced fuel to it, so this impairs         Motor Cortex function and thus performance.
    -Reduction of BCAAs and thus an increase in trytophan (and thus seratonin).
    -
Increase in Ammonia

Middle Distance Races:
-Central Fatigue to Motor Cortex via...
    -Increase in Hydrogen ions and blood lactate that causes exercise induced hyperventilation.
    -Increase in Ammonia



sources:
1- Nybo, et al. Percieved exertion is associated with an altered brain activity during exercise with progressive hyperthermia.  J Appl Physiol 91, 2001.
2-Sahlin, K. et al. Adenine nucleotide depletion in human muscle during exercise: Causality and significance of AMP deamination.  Int J Sports Med, 1990.
3- Sahlin, Metabolic Factors in Fatigue.  Exercise Metabolism, 2005.