Oxygen & O2 Carrying Capacity

For more detail, review – Chapter 9: The Pulmonary System & Exercise. IN: Katch, McArdle & Katch. Essentials of Exercise Physiology. 4th Edition. Lippincott, Williams & Wilkins, Philadelphia, 

Almost every cell in the human body requires oxygen for the production of ATP, the cell’s main source of energy. The primary function of the respiratory system (which consists of the airway, lungs, and respiratory muscles) is to provide oxygen to and remove carbon dioxide from the body tissues. This is achieved via inhalation of atmospheric gases (including oxygen) into the lungs and relying on the passive diffusion of these gases through alveolar walls and into the bloodstream. Once in the blood stream, oxygen and other dissolved gasses are transported throughout the body via the circulatory system to oxygenate all bodily tissue and perform necessary cellular functions.

1. Oxygen and Dissolved Gases

Atmospheric gas is inhaled through the airway and into the lungs. It consists mainly of nitrogen (79.04%), oxygen (20.93%), and carbon dioxide (0.03%), along with other trace elements and water vapour. In the atmosphere these elements exert what’s known as a partial pressure (measured in millimetres of mercury (mmHg) or Torr). Partial pressure is the overall pressure exerted by a specific gas; the total pressure of a system being the sum of all the partial pressures. In the lungs, partial pressure of gases is part of what drives diffusion of these gases into the pulmonary capillary network: i.e. the higher the partial pressure of a gas in the lungs the larger the volume of gas that can be dissolved within the blood. Figure 1 illustrates the dissolvability and partial pressures concept.

The ability of a gas to be dissolved within the blood also affects how much of the gas can be transported in the blood. Oxygen is poorly soluble within blood while carbon dioxide is easily dissolved within blood. Therefore, two factors – the partial pressure of the gases and ability to dissolve within blood that allows oxygen to enter the bloodstream from the lungs and carbon dioxide to exit the bloodstream into the lungs.

 Figure 1. Solution containing oxygen in water. A. when oxygen first come in contact with pure water. B. Dissolved oxygen halfway to equilibrium with gaseous oxygen. C. Equilibrium between oxygen in air and in water.


2. PaO2, SaO2 and CaO2

There are two main ways to detect the oxygen content of blood:

  • PaO2or “partial pressure of oxygen” measures the amount of free oxygen molecules dissolved in plasma (measured in mmHg or Torr). This is not always the most reliable account of the actual oxygenation state of blood as the vast majority of O2 is bound to hemoglobin. The PaO2 of an individual is determined by alveolar PO2 (PAO2) and is dependent only on lung architecture. This measurement is completely unrelated to the amount of oxygen bound to hemoglobin.
  • SaO2 or “saturation of oxygen” measures the percentage of all available oxygen binding sites in hemoglobin saturated with oxygen. There are four binding sites for oxygen on any one hemoglobin metalloprotein (hemoglobin is an iron-containing protein, hence referred to as a metalloprotein). SaO2 measurement is determined mainly by PaO2 and doesn’t reveal how much oxygen is in the blood on its own, it requires the knowledge of how much hemoglobin is in the blood as well. SaO2 is expressed in percent (%) saturation of hemoglobin. 

These two methods are a way to actively measure some parameter of oxygen in the blood. However neither measure alone, or even when combined give the actual amount of oxygen. To get the actual amount of oxygen both dissolved and attached to hemoglobin, the CaO2 must be measured:

CaO2 or “Oxygen Content” gives a definite amount of ALL the oxygen in the blood. It is the only method that takes into account how much hemoglobin is actually present in the body and uses the PaO2 and SaO2 values to get the amount of oxygen. It uses the units “ml O2/dl” (milliliters of oxygen per deciliter of blood). CaO2 is calculated the following way:

CaO2 = Hb (gm/dl) x 1.34 ml O2/gm Hb x SaO2 + PaO2 x (0.003 ml O2/mmHg/dl)

1.34 mL O2 is the amount of oxygen that can be bound to 1 g of hemoglobin
0.003 mL O2 is the amount of oxygen that dissolves in 1 decilitre (dL) of blood


3. Hemoglobin, its Properties, and the Bohr effect 

As stated above, the majority of oxygen in our blood is bound to an interesting metalloprotein known as hemoglobin (the amount of oxygen dissolved in plasma alone is only enough to keep someone alive for about four seconds, which is why hemoglobin is so important).

a) Hemoglobin

Hemoglobin is able to bind oxygen and release it to tissues when needed. This metalloprotein contains 4 heme groups each with one iron atom that are able to bind one molecule of oxygen. In addition to these heme groups, hemoglobin also contains many binding sites for various other compounds found within the blood, all of which are important for the regulation of oxygen binding and dissociation from hemoglobin.

In addition to oxygen, hemoglobin can also bind CO2 and CO (carbon dioxide and carbon monoxide) to its heme groups and transport it in the blood. This allows for quicker means of transport of CO2 to carry it away from working tissues than dissolved CO2, so CO2 can be eliminated quickly from working tissue that are creating excess CO2 (e.g. working muscles during exercise).

Hemoglobin is a fascinating molecule as it works on the basis of cooperative binding. This means that the affinity of hemoglobin for oxygen increases if a molecule of oxygen is already bound. Essentially if oxygen is bound to one of hemoglobin’s subunits then it changes the molecular structure of hemoglobin to make it more favourable to bind another molecule of oxygen. This results in the sigmoidal shape of the oxygen dissociation curve as illustrated in Figure 2. Since hemoglobin can also bind CO2 to its heme groups it results in the same cooperative binding for CO2 as it does with oxygen. Essentially it means that when CO2 is bound to hemoglobin it changes the molecular structure of hemoglobin (different from how oxygen does) to make it more favourable for CO2 binding and less favourable for oxygen to bind. The overall result of this competitive binding is faster unloading (dissociation) of oxygen from hemoglobin in areas of high CO2 concentration and faster unloading of CO2 from hemoglobin in areas of high oxygen concentration.

Figure 2. Oxyhemoglobin dissociation curve. The saturation of hemoglobin & myoglobin in relation to oxygen pressure. The white horizontal line at top of graph indicates percentage saturation of hemoglobin at the average sea level alveolar PO2 of 100 mmHg. On the right, the effects of temperature (top) and acidity (bottom) in altering hemoglobin’s affinity for oxygen (Bohr effect) are mapped.

b) The Bohr Effect

Hemoglobin is very sensitive to temperature and acidity. When the pH or temperature of the blood is altered in any way the ability of hemoglobin to bind and release oxygen is affected.

Blood becomes acidic when there is an increase in CO2 content (this relationship will be described further during your class on blood-gas analysis). Since hemoglobin is able to bind CO2 to its heme groups as well as oxygen, the two compete for the heme binding sites and the compound that is in higher concentration will generally win out. This is good news for active muscles during exercise as there is a high percentage of CO2 being produced and a low percentage oxygen remaining due to high oxygen utilization during exercise. So when oxygen rich blood encounters exercising muscle (area of high CO2) hemoglobin is put under conditions that favour the dissociation of oxygen, thus oxygen is given up readily to the working muscle. This process, as a consequence, also allows for more available binding sites on hemoglobin, for CO2 to attach and be transported out of the body much more efficiently. This effect is illustrated in Figure 2 (bottom inset panel) – what you observe is a shift in the oxyhemoglobin dissociation curve to the right in the case of high acidity (ie. high CO2 production from working muscles).

A similar effect is observed with changes in temperature. Again, taking the example of exercise, the active muscles produce heat as a byproduct of ATP production, so increase in temperature will be observed with exercise. An increase in temperature also results in a rightward shift of the oxyhemoglobin dissociation curve, and increased unloading of oxygen from hemoglobin as illustrated in Figure 2 (top inset panel). This is accomplished because an increase in temperature somewhat denatures the structure of hemoglobin, not to the point of dysfunction, but just enough so that oxygen binding is not as favorable.

These two phenomena lead to what is known as the Bohr effect. The Bohr effect shows changes in hemoglobin-oxygen binding based on the acidity (pH) and temperature of the surrounding solution. That is to say if temperature and acidity go up (increased acidity meaning a decrease in pH) the ability of hemoglobin to bind oxygen goes down. Essentially, the Bohr effect results in more efficient oxygenation of tissues and more efficient elimination of CO2 waste in the context of active tissues, which produce high acidity and high temperature in the surrounding blood.

c) Carrying oxygen to the working muscle

Oxygen is carried to the working muscle both through the dissolved oxygen but mainly through the oxygen bound to hemoglobin. The Bohr effect is particularly helpful in unloading oxygen to the working muscles during vigorous exercise, as the low pH and high temperature in the extracellular environment of the muscle fibers allows for easier dissociation of oxygen from hemoglobin.

In the muscle tissue itself, myoglobin binds to the oxygen and transfers it to the mitchondria. Myoglobin can bind to oxygen at even lower partial pressures of oxygen than hemoglobin (see Fig 2, dashed yellow line – % saturation of myoglobin is higher than hemoglobin at PO2 < 50mmHg).

People with anemia,have low iron and therefore less functional hemoglobin to carry oxygen to the working muscles, so these people will feel fatigued earlier with exercise due to a lack of oxygen being carried to their working muscles.

► CONTINUE ONWARDS TO Gas Exchange in the Lungs