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Thursday, April 23, 2015

Diffusion of oxygen from air to tissues

Today we're going to take a molecule of oxygen, and show how it travels from the air inhaled, through the lungs, the blood and then to the tissues.  Then we'll do the same for carbon dioxide, showing how it travels from the tissues to the lungs to be exhaled.

Basically, it must be understood that a gas travels from areas of high pressure gradient to areas of lower pressure gradient.  There are a couple laws of physics to help explain how this is possible.

Please note that all the numbers and percentages in this post are either estimates or averages.

Fick's First Law of Diffusion.  The rate of oxygen diffusion is proportionate to the concentration difference of oxygen and the surface area.  In other words, it travels from areas of high pressure to areas of lower pressure.  This explains how oxygen travels through tissues.

Henry's Law.  Gases dissolve in liquids in proportion to their partial pressures, depending also on how soluble they are in specific fluids and on the temperature.  This is important because most oxygen inside the body is stored in fluid, such as blood.  Inside the nose it is hunidified, and the alveoli are saturated with water vapor which has its own partial pressure.  

Total Pressure.  This is the tension given off by a molecule of a gas if it were to be confined inside a container.  The pressure is caused by movement of the molecules, and the pressure or tension they cause by constantly impacting the surface of the container.  The total pressure of a gas is summed up by the total pressure of all the molecules contained in it.

Partial Pressure.  This is the pressure exerted by a single gas component in a mixture.  It is the pressure of an individual gas of a mixture.

Dalton's Law.  The total pressure of a mixture of gases equals the sum of the partial pressures of the individual gases in that mixture. 

Room Air.  Contains about 79% nitrogen and 21% oxygen (There are other gases in the air, although they will be omitted here for to make this easier to understand).  Usually, 21% is generally designated as the Fraction of Inspired Oxygen in Room Air.  

Total Pressure of Atmospheric Air as sea level:  760 mmHg
  • Partial Pressure of Nitrogen (PN2) in room air:   600 mmHg
  • Partial Pressure of Oxygen (PO2) in room air:  160 mmHg
These pressures may vary depending on the temperature, humidity, and atmospheric pressure. 

Diffusion:  Pressure moves, diffuses, from areas of higher pressure to lower pressure.  So, by the natural process of respiration, air is inhaled.  It is humidified and warmed to body temperature by the nasal passages.  
  • PNO2 after humidified and heated to normal body temperature (37°C): 564 mmHg
  • PO2 after humidified and heated to normal body temperature (37°C):  149 mmHg
It then makes it's way though air passages to the alveoli.  

Partial Pressure of Alveolar Oxygen.  Designated as PAO2 = 104 mm Hg.  

This may be estimated by FiO2 * 5 (21% * 5 = 105).  There are other more accurate formulas, although this one is the simplest to perform in the clinical setting.  Remember that it is just an estimate using numbers that are rounded off for simplicity purposes. 

PAO2 may also be lowered due to disease processes.  As the formula suggests, the PAO2 may be higher when higher concentrations of oxygen are inhaled (or FiO2 from 22% to100%).  Likewise, less oxygen may be inhaled when breathing is relaxed while sleeping.  Less oxygen may also be inhaled due to lung disease, causing the PAO2 to become lowered.  (This may be reflected by a measure of PaO2 -- see below -- as obtained from an arterial blood gas)

Again, oxygen, unlike CO2, requires a high pressure gradient to diffuse.  

Partial pressure of capillary venous blood (PvO2) is 40

So oxygen moves from the alveoli, across the respiratory membrane, to the capillary blood because of the pressure difference:
  • 104-40 = 64 mmHg pressure difference. 
This pressure difference, or pressure gradient, is perfect for oxygen diffusion to occur from the alveoli to the capillary system.  So, oxygen molecules are released from the alveoli (PAO2 104) into the venous capillary system (PvO2 O2 40).

Inside the venous side of the capillary system is reduced hemoglobin.  This is hemoglobin that does not carry an oxygen molecule.  Since it carries no oxygen molecule, it is said to have a high affinity for oxygen. Because of this, almost as soon as oxygen enters the capillary plasma, it joins with a hemoglobin molecule. This immediately turns the capillary blood into arterial blood.

Partial pressure of arterial blood (PaO2) is 104

In the capillary system the PO2 quickly rises as more and more oxygen molecules enter the plasma.  The blood now moves pulmonary vein and then to the left atrium.  By this time, the accumulation of oxygen in the arterial system has caused a build-up of tension that causes the partial pressure of oxygen to rise to 104, the same as it was in the Alveoli.

Keep in mind that hemoglobin molecules have no impact on the partial pressure of oxygen.  This means that the PaO2, as measured by an arterial blood gas (ABG), should be about 104 (estimated to be a normal of 80-100).

Freshly oxygenated hemoglobin constitutes about 98% of cardiac output.  Another 2% of the cardiac output comes from the bronchial veins, and this blood has a PvO2 of 40.  This unoxygenated blood is shunted into the pulmonary vein, and mixes with arterial blood.  It is because of this natural shunt that a normal hemoglobin saturation is 98% and not 100%.  This in turn brings the PO2 of left ventricle down to 97 mmHg.

The saturation of arterial hemoglobin (SaO2), as measured by ABG, is normally about 98%.  The saturation of arterial hemoglocin, as measured by pulse oximeter (SpO2) is also about.

The PO2 of the left atrium:  97 mmHg

The heart contracts, and sends oxygenated blood through the arterial system.

Partial Pressure of Arterial Oxygen.  Designated as PaO2.

Because of normal variations in PAO2 (as explained above), the PaO2 may likewise vary.  So, that said, the following is generally considered as true of PaO2. 
  • Normal: 80-100
  • Hypoxemia:  60-80
  • Severe Hypoxemia:  40-60
So now, the oxygen molecule is attached to a hemoglobin molecule.  Hemoglobin now has a low affinity for oxygen.  It rides the bloodstream until it finds a cell that has a low enough PO2 for it to diffuse into that cell.  The cell then has a higher affinity for oxygen than the hemoglobin molecule, and so oxygen is released into the cell tissue. Here the oxygen molecule is used to create energy.

Partial Pressure of Tissue Oxygen.  
  • Varies from tissue to tissue
  • Some tissues have a PO2  of 22-35
  • The PO2 varies in different areas of a cell
Once oxygen leaves the arterial system, this leaves the hemoglobin in venous blood without oxygen. This blood then returns to the lungs via the venous system to get some more oxygen. 

Partial Pressure of Venous Oxygen. Designated as PvO2, is 40.

Now the system starts all over again.  However, if we determine that the patient has a disease process that causes hypoxemia (defined as PaO2 less than 60), and the patient is given a higher FiO2 than what is in room air (22% to 100%), the rate of diffusion of oxygen from the lungs to the tissues will increase.

Once in the cell, the oxygen is quickly absorbed into the mitochondria and is used as part of cellular respiration.  Energy is the byproduct, and this allows the cell do perform its work.  A wasteproduct is Carbon Dioxide (CO2)

About 200 ml of CO2 is produced by each cell per minute. This CO2 has to be quickly eliminated from to prevent acidosis.  CO2 is 20 times more soluble than oxygen, and therefore diffuses quickly. Likewise, while oxygen requires a high pressure gradient to diffuse, CO2 requires only a small pressure gradient.

Partial Pressure of  Venous Carbon Dioxide (PvCO2):  46 mm Hg

Partial Pressure of Alveolar Carbon Dioxide (PACO2): 40 mmHg

Partial Pressure of Arterial Carbon Dioxide (PaCO2):  40 mmHg

Partial Pressure of Room Air Carbon Dioxide:  0.2

So even while the pressure gradient between the venous system and alveoli is only 6, this is enough for CO2 to diffuse through the system.

Therefore, under normal conditions, CO2 is easily diffused through the body, and exhaled.  Oxygen is inhaled and easily diffuses through the body to the cells.  Of course, effecting these are atmospheric variations like humidity and temperature, disease processes like COPD, and aging.

References and further reading.

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