- 1 Aerobic fitness
- 2 Oxygen transport to the mitochondria
- 3 Mitochondrial use of O2
- 4 Measuring oxygen consumption
- 5 The components of aerobic fitness – measure patient fitness
- 6 Determining the Ventilatory Threshold (VT)
- 7 Aerobic capacity of the Australian population
- 8 Aerobic fitness: limiting factors
- 9 Respiratory function and ventilation
- 10 Cardiovascular function
- 11 Skeletal muscle considerations
- 12 Functional implications of low aerobic fitness (VO2max)
- 13 Intervention: the effect of physical activity on aerobic fitness
Aerobic fitness – the capacity to use oxygen for energy production.
- Assessed through maximal oxygen consumption measurement (VO2max)
- Can be normalized by body weight:
- [Absolute VO2max] VO2max in L/min or
- [Relative VO2max] VO2max in mL/kg/min (volume unit shrunk due to normalization per kg)
- Highly dependent on
- 1) the capacity to transport O2
- a) from the environment into your blood and
- b) in the blood to target organs and
- 2) the capacity to use it in those organs
- This is because the VO2max reflects the capacity to use O2 to generate energy.
- 1) the capacity to transport O2
- Mainly the muscles determine your VO2max. The mitochondria inside the muscles are the site where oxygen is used, so any factor that determines the transport of oxygen from the air to your mitochondria is critical in determining your VO2max. Hence diseases that affect your heart/lungs/vascular system/muscle might impact on your VO2max
Oxygen transport to the mitochondria
- Step 1: Extract oxygen from the external environment and transfer to the lungs, reach the alveoli, where it will diffuse to the cardiovascular system
- Step 2: CV system transports oxygen to your tissues in the cardiovascular system, to your muscles
- Step 3-4: Transport to the muscle, where O2 is used in the mitochondria as an electron acceptor to produce ATP (reducing the O2 to water).
Every step here is critical. Alteration in any of these steps will affect your oxygen consumption and your VO2max.
Mitochondrial use of O2
- Once in the mitochondria, there are different substrates that can be used as a source of energy. Glucose and lipids are the ones we focus on here, but protein/amino acids can also be used
- Lipid taken up into the mitochondria can be broken down by beta-oxidation into acetyl CoA, which is fed into the TCA cycle. This can only be done in aerobic exercise. (Lipid metabolism needs oxygen).
- Glucose can also be used as a substrate and can be broken down into acetyl CoA to be used in the TCA cycle. However, glucose can also be used in anaerobic conditions (unlike lipids). This produces ATP only through 1) glycolysis and 2) the subsequent conversion of pyruvate to lactate. (Glucose metabolism can use oxygen or use no oxygen).
- Hence fat people need to restore a certain mitochondrial density in order to be able to use fat as a substrate to lose weight through exercise.
Measuring oxygen consumption
- The most accurate way to measure oxygen consumption is to put a catheter in the aorta and to measure the arterial oxygen concentration (to work out how much oxygen is carried in the body), and do the same thing in the vena cava (to measure what oxygen is used). However, this is very uncomfortable. Then the muscle oxygen consumption is given by:
Oxygen consumption = Arterial oxygen concentration - Venous oxygen concentration
- Although we now have less invasive measurements, the target measurement we want is the difference in arterial and venous oxygen concentration. This lets us know how much O2 is used in muscles and how much remains in the blood to be recirculated.
- A better (less invasive) measure is calculated using the difference in oxygen concentration in inspired and expired air. This is given by:
Oxygen consumption = Oxygen concentration in inspired air - Oxygen concentration in expired air (approximately)
- Patient is put on a bike, and you ask the person to cycle at different intensities. The protocol is:
- Progressively increasing intensities
- 1-minute cycles
- First 4-5 minutes are almost painless (relatively easy)
- Push the patient to their max between 8-12 minutes
- The last few minutes are more difficult, where you reach a maximum exertion
- All variables measured:
- VO2 (oxygen consumption; mL/min)
- VCO2 (carbon dioxide production; mL/min)
- VE (ventilation; the total amount of air that enters your lungs per minute; L/min)
- HR (heart rate; beats per minute)
- Intensity of exercise (watts)
- Variables graphed:
- Red = VO2 (oxygen consumption; mL/min)
- Blue = VCO2 (carbon dioxide production; mL/min)
- Green = VE (ventilation; the total amount of air that enters your lungs per minute; L/min)
- These are measured through gas analyzers, that measure [O2] and [CO2] in inhaled and exhaled air.
- At rest, we have steady variables
- 60 W training is a warm up. The body adapts quickly to the requirement, corresponding to a plateau in parameters (the ventilation, VCO2 and VO2 all remain constant).
- As we gradually increase the intensity, there is a steady increase in all parameters.
- At a particular intensity, the VO2 will plateau, while ventilation dramatically increases (hyperventilation). Even if the patient exercises harder (by increasing the resistance on the bike), the oxygen consumption does not increase.
- At this stage, there is a transfer in dominance from aerobic to anaerobic respiration (the fact that oxygen consumption peaks DOES NOT mean that the patient will die or faint, just that the predominant energy-generating biochemical process has changed. The patient can no longer supply all of the energy needed for the exercise through their aerobic pathways, as these have been maxed out. Thus they bolster energy output with auxiliary anaerobic metabolism).
- When the patient reaches this plateau level, he will reach a maximal heart rate. The maximum heart rate is given by
Maximum heart rate = 220 – Age of patient
The components of aerobic fitness – measure patient fitness
- Maximal component of aerobic fitness = VO2max (discussed above)
- Submaximal component of aerobic fitness = Ventilatory threshold (VT), which can be understood as follows:
- Looking at the green curve, there is an approximately linear increase in VE with time, up to a certain level.
- At a certain level, there is an exponential increase in VE
- The breakdown in the relation is the ventilatory threshold, where the patient starts to hyperventilate
- This is the point at which there begins to be a significant contribution of anaerobic respiration to the production of energy (ATP), and production of lactic acid (as pyruvate → lactate)
- To buffer this decrease in pH, you will need to generate water and CO2 (to make bicarbonate), and this increased CO2 is what drives the increase in ventilation.
Determining the Ventilatory Threshold (VT)
- When carbohydrate or fat is oxidized using oxidative phosphorylation:
VO2 = VCO2 (as the number of O2 molecules used is the same as the number of CO2 molecules produced)
- When increasing intensity, we need to provide energy quicker. This means it takes too long to go through all the aforementioned steps (1 – 4) in transporting and using oxygen to produce energy. Therefore increasing intensity causes reliance on glycolysis (which is faster and local). Glycolysis results in more CO2 production, which increases ventilation. Further down the track, hyperventilation will follow.
- Therefore the indicators of the level at which the patient is exercising include:
- 1) Whether or not they are hyperventilating
- 2) The respiratory quotient (RQ) or respiratory exchange ratio (RER):
RQ = VCO2/VO2
This is indicative of the type of substrate being oxidized:
- 0.7 = mainly fat (low intensity, fasting conditions)
- 1 = mainly carbohydrate (high intensity)
- This corresponds to a breakpoint in the relationship (see graph to the right) of VCO2 vs VO2
- Once the VT is determined, note the HR at which VT was reached. This is a further indicator of the level of fitness of the patient.
Aerobic capacity of the Australian population
- This table shows the aerobic fitness of the Australian population as given by the relative VO2max (normalized to body mass)
- Males have a higher relative VO2 max compared to females due to higher muscle mass
- With ageing, even if you keep on exercising, your VO2max will continue to decrease (10% per decade, or 1% per year)
- If you exercise, you can preserve your VO2 to a greater extent and slow down the ageing, but ageing will always have a negative impact on VO2max
- People with a poor VO2max have a higher risk of being affected by certain diseases (diabetes, metabolic syndrome, cardiovascular disorders).
- Even an average aerobic fitness can become critical after the age of 60 years, increasing the risk of being afflicted by certain diseases. For example, older may people start hyperventilating when trying to cross the street in the time allowed by the green light. Having a poor VO2max has a negative impact on both mortality and morbidity, as well as quality of life.
Aerobic fitness: limiting factors
- O2 uptake into the lungs
- O2 diffusion from the alveoli to the circulation
- There is an imbalance between the alveoli that receive oxygen and those that will be perfused by capillaries. Not every single alveolus will receive oxygen, and not every one will be perfused by the circulation. Therefore there is an imbalance between ventilation and perfusion. Normally this won’t effect your VO2max. In certain situations (eg emphysema) where you have a massive destruction of your alveoli, the capacity to retrieve oxygen from your lungs to your cardiovascular system will be impaired, severely impacting on your aerobic fitness.
- O2 delivery by the cardiovascular system (heart, vessels, red blood cells)
- This involves the capacity of the heart to pump blood through your system
- Also involves the appropriate relaxation of the vessels to allow blood to flow through the cardiovascular system
- Also depends on the level of red blood cells (haematocrit) in the blood, as they are the medium by which oxygen is transported around the body. Someone with kidney failure has very low haematocrit, impacting on the capacity to transport oxygen.
- Cyclists take EPO to increase red blood cell production and to increase the haematocrit, the capacity to transport oxygen, and hence the VO2max.
- O2 diffusion from the vessels to the muscles
- This depends on the differential pressure of O2 between the vessels and the muscles
- O2 uptake and consumption by the muscles
- Mitochondrial density is critical to oxygen consumption
- Slow twitch fibres = high density of mitochondria; very high oxidative capacity; endurance training increases the percentage of slow twitch fibres. If you don’t exercise, not only do you lose muscle mass, but you also preferentially lose slow twitch fibres. Therefore you decrease your oxidative capacity overall.
Respiratory function and ventilation
- Ventilation is the main parameter we’re interested in with regard to the health of the respiratory system
- Ventilation (VE) = volume of air you can breathe per minute (L/min)
- The ventilation produced during exercise determines (to a certain point) the capacity to transport oxygen or extract oxygen from the ambient air and transport it through the cardiovascular system. (Note however that there is also the alveolar/arteriolar diffusion to allow the O2 to enter the bloodstream)
- In sedentary people, the maximum ventilation (VEmax) = 100-120 L/min
- Maximal voluntary ventilation (MVV) is a measure of the maximum amount of air that can be inhaled and exhaled within one minute (for the comfort of the patient this is done over a 15 second time period before being extrapolated to a value for one minute, expressed as L/min). This is approximately equal to FEV1*35
- Forced Expiratory Volume in 1 second (FEV1) is the volume exhaled during the first second of a forced expiratory maneuver started from the level of total lung capacity
- The maximal ventilation a sedentary person will reach during exercise (as mentioned above) will be 100-120, and that is far lower than your maximal voluntary ventilation
- When you exercise and reach maximal oxygen consumption, you reach about 80% of your respiratory reserve volume
- Thus the lungs are oversized with respect to the demand during exercise: you could push harder if the lungs were the limiting factor during exercise
- The cardiovascular system determines the amount of oxygen that is transmitted through the circulation and into the muscles.
Main cardiovascular determinants
- Heart rate (HR, bpm) – maximal heart rate is the limiting rhythm when you exercise
- Stroke volume (SV; mL) – the amount of blood pumped in each systole
- Cardiac output (Qc; L/min) – the amount of blood that the heart can pump per minute
- Since Qc = HR * SV, then any alteration in heart rate (HR) or stroke volume (SV) will affect your cardiac output (Qc)
- A patient taking a beta blocker will have a heart rate plateau at 130 bpm (independent of age), hence there is a reduced capacity to increase your cardiac output, lowering aerobic fitness
- A patient who has had a myocardial infarction and had massive necrosis of the left ventricle will have a reduced stroke volume, and this will also reduce cardiac output and aerobic fitness
- The relationships between VO2 and SV, and VO2 and HR are shown in the diagram to the top-left. A linear relationship is observed.
- Hence the cardiovascular system is very important to the VO2max (the maximal oxygen consumption during exercise). [Although we haven’t yet determined that it is the limiting factor]
Isolated exercise and cardiac output
- When only cycling (without arm involvement), there is a certain cardiac output that corresponds to a certain blood flow to the legs (since the legs are the exercising muscle)
- Exercising using one leg, a certain VO2 (oxygen consumption) will be reached. When exercising using two legs, the VO2 will increase
- When arm involvement is introduced, there is a further increase in cardiac output. There will be a decreased length of flow between the heart and the arms, however VO2max still increases.
→ Cardiac output is related to muscle blood flow and oxygen uptake.
- Hence if you increase the muscle mass that is exercising, then further work from the heart is required, resulting in a further increase to the VO2max. Some muscles will actually receive less oxygen.
Increased active muscle mass → Decreased blood delivery to active muscles.
- This indicates the fact that the cardiovascular system is the limiting factor here, because if the cardiac output cannot increase, then neither can the VO2max increase further, since even a reduction in blood flow to a specific muscle doesn’t reduce the VO2.
Cardiac output (Qc) limits oxygen consumption (VO2)
- Improving the delivery of oxygen to muscles (using EPO treatment) gives a significant increase in VO2max
- The limiting factor of aerobic fitness (measured by VO2max) is the ability of the cardiovascular system to deliver oxygen to the active muscle/s.
Skeletal muscle considerations
- The VO2max during one-legged exercise is about 300 mL/kg/min
- Oxygen consumption increases with increasing intensity
- VE and HR only slightly increase with increasing intensity
- Oxygen consumption of the muscle is 3 times higher when compared to the VO2 of the same muscle mass during cycling
- Hence during cycling, the limiting factor of oxygen consumption (VO2) was not the ability of the muscles to use the oxygen
- During exercise involving large muscle mass, there is competition between the different exercising muscle groups for O2 delivery
- The critical factor is not the capacity of the muscles to extract or use the oxygen, but the limiting factor is the bloodflow that reaches the muscles
Functional implications of low aerobic fitness (VO2max)
- There is an obvious relationship between aerobic fitness and mortality rate (also between physical activity and mortality rate).
- Hence aerobic fitness VO2max is a risk factor for morbidity and mortality
- Some people benefit more than others from training. There is a genetic component to this: some people are good responders to exercise, while others respond less.
- [Grey/white graph to the right] In people with pre-existing conditions, there is a direct link between the relative risk of death and aerobic fitness
- Note that here the MET (metabolic equivalent) is used as a measure of aerobic fitness instead of VO2. 1 MET is the average VO2 at rest: 3.5 mL/kg/min. It corresponds to the resting metabolic rate (RMR).
- This value is individual and can vary – the more muscle mass you have, the higher the RMR.
- However, 1 MET has been set to 3.5 mL/kg/min by convention
- Low aerobic fitness is a major risk factor for the development of the most prevalent chronic conditions (major cardiometabolic conditions) in our society.
- People who are hospitalized are unable to exercise and this impacts negatively on their level of aerobic fitness. At some point, hospitalization will therefore contribute to the increased risk of mortality.
- Even in normal subjects, low aerobic fitness represents a major risk factor for increased mortality (decreased survival rate). [Also applies to people who have a chronic disease]
Intervention: the effect of physical activity on aerobic fitness
- No major effect of exercise on HRmax. If you don’t have a pre-existing condition, it shouldn’t change very much.
- At a sub-maximal level of exercise, the demand on your heart will be lower, and the heart rate will be lower. At the same intensity pre- and post-exercise, your heart rate will be lower (indicating the progress you are making)
- Increased cardiac contractility and adrenergic sensibility
- Stroke volume increases at both maximum and submaximum levels of exercise
- Increased blood (plasma) volume (more blood in the circulation, so we can fill more into the left ventricle)
- Increased size of left ventricle (adaptation to exercising the heart; increases the capacity of the heart to contract during systole)
- The above two factors will impact on and improve the cardiac output, Qc
- This also increases the O2 pulse (the oxygen delivery to active muscles)
- Overall, VO2max increases
- ⇒ Regular exercise improves your VO2max
Further adaptations to exercise
- Diagram to the right shows a direct relationship between VO2max and the capacity of the mitochondria to utilize oxygen (the oxidative capacity of the muscles). Training causes your muscles to use more oxygen (⇒ an increase in mitochondrial density).
- Enzymatic activity of the muscle cells and the mitochondria also increases
- This trains the muscles to use oxygen, but also to use fat as a substrate.
- Another adaptation is the relative level of VT compared to VO2max.
- One is unable to sustain exercise at VO2max for more than about 6 minutes. One is able to sustain exercise at VT for hours (at least 2 hours).
- In a sedentary population, VT is about 40-50% of VO2max. Above VT, they start to hyperventilate and cannot exercise for long (they cannot reach high oxygen consumption for a long time).
- Elite athletes have a VT that is about 85-90% of VO2max, and so can exercise at this high level of oxygen consumption for hours.
- Therefore further adaptations to training are:
- Increase of VO2max
- Increase of VT
- An improvement in the relative percentage of the VT compared to the VO2max.
- Someone who is constantly exercising above VT (because their aerobic fitness and VT are low), will be disinclined to want to exercise. Improving aerobic fitness and the VT will mean that the patient will be able to exercise at high intensities without the painful feeling of hyperventilation, or feeling worn out.
- This improvement of VT compared to VO2max is explained by improved mitochondrial density, oxidative capacity, and resulting an improved capacity to oxidise fat.
- People who are well trained can lose more fat. Unfair! It is more painful for fat people to lose fat, but exercise has positive feedback on fat loss.
Before and after training
- Pre-training: A set capacity of lungs, cardiovascular system, circulation and muscles to transport (and, later, use) oxygen
- Post-training: In a healthy person, there is usually no improvement in lung capacity (unless bronchoconstriction prior to training). Improvement in cardiovascular system, improved transfer from circulation to the muscle, and improved ATP production in the muscle.
- The above factors have an impact on the capacity to oxidise fat and glucose, and this will affect on most of the risk factors of developing cardiovascular conditions.
- Better capacity to relax vessels → reduced hypertension (short-term resting blood pressure reduction is an acute effect of exercise)
- Improved lipid and glucose profile (long-term, you train your muscles to consume lipids and clear them from the circulation). Skeletal muscle accounts for about 80% of glucose clearance from the circulation. If the muscles become insulin resistant, this glucose will stay in the circulation (causing development of hyperglycaemia). Muscle contraction can impact on glucose uptake in an insulin independent way (even someone who has late-stage insulin resistance will still benefit from exercising – the simple fact of exercising the muscle will support the consumption of glucose).