Here's what you need to know about the respiratory membrane

Once in the lungs, various elements effects oxygen's ability to cross the alveolar-capillary membrane, which is also known as the respiratory membrane. In my post "Diffusion of oxygen from air to tissues" I described how oxygen travels from the lungs to the tissues.

The ability of oxygen to cross the alveolar-capillary (respiratory) membrane depends on.

1. Rate of diffusion of oxygen across the respiratory membrane.  
2. Pulmonary Capillary Blood Volume or Flow 
3. Transit time
4. The ability of O2 to bind with Hemoglobin (Hgb)

1.  The rate of diffusion across the respiratory membrane is determined by.

• Thickness of the respiratory membrane (disease processes may damage it).  
• Normal thickness: 0.4-0.6 micrograms (sometimes as low as 0-.2 micrograms)
• Pulmonary edema, fibrosis, deposition of substances, may increase thickness
• Surface area of the respiratory membrane 
• Total capillary-alveolar surface area in normal, healthy person is 70 square meters.  
• There are over 300 million alveoli
• There is usually about 60-140 ml of blood in pulmonary capillaries
• This allows for plenty of surface area for oxygen to diffuse from alveoli to capillaries.
• Diseases like emphysema greatly reduce surface area for gas exchange to occur.
• The diffusion coefficient of gases (oxygen)
• This is essentially how soluble is the gas in water, as it has to go from alveolar air to capillary blood, a solution. 
• Solubility coefficient = concentration of dissolved gas + partial pressure (no need to memorize this)
• CO2 is 20 times more soluble than Oxygen, so CO2 diffuses 20 times more rapidly across the respiratory membrane as oxygen does.  
• The difference between alveoli (PAO2) and capillary (PcO2).  PAO2 is 104, and venous blood is 40.  This results in a pressure gradient of 64 mm Hg. 

2.  Pulmonary Capillary Blood Volume or Flow is determined by.

• Capacity of blood, especially red blood cells
• Polycythemia: Oxygen diffuses at a higher rate
• Anemia: Oxygen diffuses at a lower rate

3.  Transit Time is determined by. 

• Determined by dividing pulmonary capillary blood volume by cardiac output.  
• Normal Transit Time: 70 ml divided by 5,000 = 0.8 seconds
• This is the time available for diffusion to occur. 
• Most diffusion occurs in first 0.3 seconds of Transit Time
• This leaves 0.5 seconds, providing a large safety margin.  This explains why adequate oxygenation can still occur when a person is exercising, even thought the transit time is reduced to 2/3 of normal, or 0.1 seconds. 

4.  Capacity of binding of Oxygen with Hemoglobin is determined by.

• This is a discussion for another day, and we will not go there.

Normal Arterial Oxygen Tension can be calculated. 

• A-a Gradient:  PAO2 - PaO2
• 104-97 = 7 mm Hg
• Normal is below 15 mm Hg
• Normal range is 5-25
• Upper range may increase with age to 20 or even 30
• The following formula allows you to determine A-a Gradient adjusted for age.
• PaO2 = 102 - Age/3
• Depends on.
• Ventilation (V) 
• Perfusion (Q) 
• Shunt (Mixed venous blood)
• Is the main cause of hypoxemia (drop in PaO2) and hypercapnea (increase in PaCO2)
• V/Q Mismatching:  Oxygen is inhaled but cannot get to the blood in certain areas of the lungs.  
• Shunt: Blood doesn't come into contact with alveoli, blood is shunted away from alveoli.  No gas exchange occurs.  
• True Shunt (anatomical). Natural shunts that purposefully bypass the lungs, such as the shunt noted above whereby unoxygenated blood from bronchial veins is shunted to the pulmonary artery. 
• False Shunt (physiological).  This is where blood is supposed to come into contact with an alveoli, but this cannot happen due to a disease process.
• The best indicator of a shunt is PaO2.  This is because a small reduction in O2 results in a large reduction in PaO2 (about 7 mm Hg).  A small increase in CO2 results in a small increase in PaCO2 (less than 1 mm Hg)
• Up to the presence of a 50% shunt, Increases in FiO2 will have no effect on PaO2

Why is a normal SpO2 98%?

Question:  Why is a normal oxygen saturation 98% and not 100%?

Answer:  After the diffusion of oxygen from the alveoli to the capillary occurs, this oxygenated blood moves to the pulmonary vein to the left atrium.  This blood contains a PaO2 of 104, on average.  This blood constitutes 98% of cardiac output.  Another 2% of the cardiac output comes from the bronchial veins, and this blood has a PaO2 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 saturation is 98% and not 100%.

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.

• Oxyhemoglobin Dissociation Curve Made Easy
• Textbook of Anesthesia for Postgraduates, edited by T.K. Agasti, pages 43-48
• Cardiovascular Physiology Concepts, By Richard Klabunde, pages 182-183
• Respiratory Therapy Formulas

Myth Buster: A high FiO2 is protective

So you have a patient come into the emergency room in severe respiratory distress, possibly heart failure, but the SpO2 is normal. In the past it was acceptable to place these patients on a nonrebreather to prevent the patients condition from deteriorating, thus allowing you time to react. This, however, may no longer be acceptable.

I think doctors have gotten much better at not panicking in this regard, as even patients with heart failure, while the used to always get a nonrebreather, that seems to no longer be the case. As with chest pain and any other condition, no oxygen is given unless the SpO2 drops below 94%.

The reasoning for the change was described in an October, 2013, article in Respiratory Care, by Thomas Blakeman.  He said:

According to Downs, the only true indication for prophylactic hyperoxyxgenation is prior to tracheal intubation. Downs furher states that, hypothetically, a patient on FiO2 of 100% and having a PaO2 of 650 m Hg, could drop to 90 mm Hg due to lung function deterioration over a period of 15-20 minutes, but the SpO2 would not drop below 98%. This drop would not be enough to indicate a problem. But over the next 5 minutes the SpO2 wold drop to 92%, alerting the caregiver to investigate. In this scenario the elapsed time until a problem is detected would be 20-25 minutes. If that same patient was on an FiO2 of 30% with a PaO2 of 90 mm Hg and an SpO2 of 99% and experienced the same problem, the SpO2 would decrease to 94% within 10 minutes, alerting caregivers to a problem much earlier. Additionally, if a patient is already receiving FiO2 of 100%, there is no room to increase once a problem is detected."

So, over-oxygenating, a common occurrence in hospitals, may mask an underlying problem, delaying treatment.

References:

1. Blakeman, Thomas C., "Evidence for Oxygen in the Hospitalized Patient: Is more Really the Enemy of Good," Respiratory Care, October, 2013, volume 58, number 10, pages 1679-1693

RT Cave Facebook Page
RT Cave on Twitter

Myth Buster: FiO2 less than 60% is safe

One of the myths of respiratory therapy is if we get the FiO2 down to 60% we are safe.  In fact, most of us were taught in school that an FiO2 greater than 60% produced more side effects than an FiO2 less than 60%.

This apparently is a myth, and the following is the evidence:

1. Register et al conducted a study with subjects under going open heart surgery, all of whom were breathing room air preoperatively  It was found that in subjects administered FiO2s of 0.50 postoperatively had a greater degree of hypoxemia on room air on postoperative day 2 than those given sufficient oygen to maintain SpO2 (greater than) 90%.  After repeating the study using only room air intra- and post-operatively, and finding that most subjects did not have a decrease in blood oxygen levels, as compared to preoperative values, it was postulated that the hypoxemia experienced in the first study was due to the use of oxygen during and after surgery.

1. Garner et al exposed rats with peritonitis to FiO2 of 0.80, 0.4, or 0.21. Mortality was lowest in the FiO2 O.21 group, and highest in the Fio2 0.80 group.  Upon postmortem examination it was found that lung pathology did not differ between the groups but there was substantial liver damage with FiO2 (greater than) 0.21.  It was postulated that free radical formation caused the liver damage. 

This is yet another example that oxygen should not be administered unless necessary, and that every effort should be made to reduce oxygen as soon as possible.  Thankfully, most hospital oxygen protocols call for maintaining an SpO2 of somewhere in the range of 88-94%.  

References:

1. Blakeman, Thomas C., "Evidence for Oxygen in the Hospitalized Patient: Is more Really the Enemy of Good," Respiratory Care, October, 2013, volume 58, number 10, pages 1679-1693

RT Cave Facebook Page
RT Cave on Twitter

Myth Buster: Routine use of oxygen is safe

There is now ample evidence that oxygen is a drug with side effects.  No longer should health care providers administer oxygen under the philosophy "it may not help, but it won't hurt."

Oxygen used to be considered useful, or at least harmless, for any of the following situations, despite lack of evidence it does any good:

• Emergency departments
• Post-anasthesia care units
• Conscious sedation
• Chest pain
• Shortness of breath
• Critical Care Units

ACLS used to recommend 2-4lpm by nasal cannula for chest pain. The idea here is that if a low flow of oxygen to the heart is causing the chest pain, the oxygen "might" help.  

However, there was never any science to show this.  Plus, it makes no sense, because if you are getting an SpO2 reading of 98%, then you know the heart has an ample amount of oxygen.  If it's not getting enough oxygen it's because of a blockage in the coronary arteries, not the supply of oxygen to the heart. 

ACLS currently recommends oxygen only if the SpO2 is less than 94%.  This makes much more sense to me.  

Plus, most hospital-wide oxygenation protocols call for an SpO2 of 90-94%, and even 88% is often acceptable.  This makes sense particularly if you look at the deoxyhemoglobin curve.  

One of the main reasons why it's important not to oxygenate until the SpO2 decreases is that the use of supplemental may mask that an underlying problem may be occurring.  

A patient may have decreased ventilations, but this will not be recognized because the SpO2 is already artificially maintained with supplemental oxygen.  When such a patient is not on oxygen, a dip in SpO2 would be noticed at a routine check, and oxygen could be administered at this time, with appropriate measures being taken to recognize and resolve the underlying cause. 

The new policies make sense, especially when you consider that oxygen is a drug with side effects and an expense. To oxygenate based on a myth that it will help but won't hurt is not good medicine. 

References:

1. Blakeman, Thomas C., "Evidence for Oxygen in the Hospitalized Patient: Is more Really the Enemy of Good," Respiratory Care, October, 2013, volume 58, number 10, pages 1679-1693

RT Cave Facebook Page

RT Cave on Twitter

Benefits of NIV for COPD-CO2 retainers

Citing previous studies, Augusto Savi, et al lists the following as the advantages of using noninvasive ventilation for chronic obstructive pulmonary disease (COPD) patients presenting with respiratory distress. T

1. Increases tidal volume
2. Improves CO2 elimination
3. Reduces respiratory drive
4. Reduction in treatment failure
5. Lower mortality
6. Fewer complications
7. Lower intubation rate

However, they note the following:

In these patients CO2 elimination was increased but overall ventilation-perfusion mismatch is not changed during NIV.  A more important effect is the unloading of the respiratory muslces, which are often close to fatigue in severe episodes of respiratory failure.  

Furthermore, they note the following regarding the safety of oxygenating these patients:

Crossley et al concluded that CO2-retaining COPD patients following a period of mechanical ventilation with PaO2 in the normal range can safely receive supplemental oxygen without retaining CO2 or a depression of respiratory drive.  A new ventilation-perfusjion relationship is established during ventilation to normoxia, and is not altered by further increasing the FiO2.  Nevertheless, the safety of oxygen supplementation during NIV in CO2-retaining COPD patients is not clear.

So it is quite clear that NPPV greatly benefits COPD patients in respiratory distress, and, likewise, there are no harmful effects of oxygenating them as needed to prevent hypoxia.

References:

1. Savi, Augusto, et al, "Influence of FiO2 During Noninvasive Ventilation in Patients with COPD," Respiratory Care, March, 2014, Volume 59, Number 3, pages 383-387

RT Cave Facebook Page

RT Cave on Twitter

ABG interpretation made easy: Oxygenation

An arterial blood gas can help you determine how well patient is oxygenating. Essentially, all you have to do is memorize the following chart.

	PaO2	SpO2
Normal	80-100	95-99%
Mild Hypoxemia	60-79	90-94%
Moderate Hypoxemia	40-59	75-89%
Severe Hypoxemia	< 40	< 75%

Oxygen Therapy.  Using oxygen therapy to improve oxygenation.  It generally involves inhaling an FiO2 greater than that which is contained in room air.

Fraction of Inspired Oxygen (FiO2).  This is the percent of oxygen in the air inhaled.  Room air contains 21% FiO2.  Oxygen Therapy may supply an FiO2 from 22-100%, depending on the device used. To learn more, check out "Oxygen Therapy Made Easy."

Goal of Oxygenation.  Most protocols now recommend the least amount of supplemental oxygen to maintain an SpO2 of 90% and a PaO2 of 60.  For some patients with lung disease, lower SpO2s may  be acceptable. For instance, with some cases of advanced COPD, an SpO2 of 88% may be acceptable.

Responsive Hypoxemia.  Supplemental oxygen improves oxygenation levels.  Or, increasing FiO2 increases SpO2 and PaO2 to acceptable levels.

Refractory Hypoxemia.  Supplemental oxygen does not improve oxygenation levels.  Or, increasing FiO2 does not result in an increase in SpO2 and PaO2.  It's commonly described as an SpO2 of less than 60 despite receiving 100% FiO2.

Hypoxemic Respiratory Failure.  Failure of the heart and lungs to oxygenate the blood despite the application of supplemental oxygen via oxygen therapy.

• PaO2 less than 60 on 50% or greater FiO2
• PaO2 less than 40 on any FiO2

Desired FiO2.  Calculated:  Desired PaO2 + Known FiO2 divided by known PaO2

How to use ABG results to determine if oxygen therapy is working over time. 

1. Expected PaO2 = FiO2 * 5
• Example.  If a patient is on 100% oxygen, you should expect a PaO2 of 500.  If the PaO2 is only 200, you know the patient is not oxygenating well.  
2. Actual PaO2/ Expected PaO2 = % of patient expected PaO2:
• Should be recorded daily 
• Shows if patient is oxygenating better
• Better indicator than simply looking at actual PaO2 and FiO2
• Normal = zero (patient requiring no supplemental oxygen)

Examples of % expected PaO2: (Despite lower PaO2, patient still oxygenating better)

• January 1 PO2 40 on 100% FiO2 = 80%
• January 5 PO2 60 on 40% FiO2 = 30%
• January 6 PO2 55 on 50% FiO2 = 20%

Another example of % expected PaO2 (PO2 look good, but is patient really oxygenating?)

• January 1 PaO2 200 on 100% FiO2 = 40%
• January 5 PaO2 100 on 100% = 20%
• January 6 PaO2 100 on 90% = 22%
• January 10 PaO2 55 on 80% = 13%

You don't necessarily need to use these formulas to see if patient oxygenating well, yet sometimes they can be useful. Especially for the more complicated cases, it helps to see the numbers and the trends.

Post originally published on 8/11/10 on respiratory therapy cave; updated by Rick Frea for accuracy and simplicity.

Further Reading

• ABG interpretation made easy: interpretation of acid base balance 
• The ABG lexicon
• Learn about the 4-5-6, 7-8-9 rule
• Oxyhemoglobin Dissociation Curve
• How to know if your patient is a CO2 retainer
• Cord Blood Gases made easy
• The argument against ABGs
• What is an ABG
• Respriatory Therapy Formulas

RT Cave Facebook Page
RT Cave on Twitter