The alveolar gas equation is used to calculate alveolar oxygen partial pressure as it is not possible to collect gases directly from the alveoli. The equation is helpful in calculating and closely estimating the PaO2 inside the alveoli. The variables in the equation can affect the PaO2 inside the alveoli in different physiological and pathophysiological states.
Patm is the atmospheric pressure (at sea level 760 mm Hg), PH2O is partial pressure of water (approximately 45 mm Hg). FiO2 is the fraction of inspired oxygen. PaCO2 is partial pressure of carbon dioxide in alveoli (in normal physiological conditions around 40 to 45 mmHg). RQ is the respiratory quotient. The value of the RQ can vary depending upon the type of diet and metabolic state. RQ is different for carbohydrates, fats, and proteins (average value is around 0.82 for the human diet). Indirect calorimetry can provide better measurements of RQ by measuring the VO2 (oxygen uptake) and VCo2 (carbon dioxide production).
RQ = amount of CO2 produced/amount of oxygen consumed
At sea level, the alveolar PAO2 is:
The 3 major variables of the equation are the atmospheric pressure, amount of inspired oxygen, and levels of carbon dioxide. Each has an important clinical significance and can help explain different physiological and pathophysiological states.
The function of the alveolar gas equation is in calculating alveolar-arterial O2 gradient (A-a gradient).
Estimating A-a gradient:
A-a gradient increases 5 to 7 for every 10% increase in FiO2.
The arterial PO2 can be determined by obtaining an arterial blood gas. With the help of the alveolar gas equation, the partial pressure inside the alveoli can be calculated.
Carbon dioxide is a very important variable in the equation. The PO2 in alveoli can change significantly with variations in blood and alveolar carbon dioxide levels. If the rise in CO2 is significant, it can displace oxygen molecules which will cause hypoxemia.
As atmospheric pressure reduces with increased altitude, the alveolar gas equation helps to calculate the PAO2 within the alveoli. This is significant to appropriately identify the developed hypoxemia from decreased atmospheric pressure and subsequently treat with appropriate supplemental oxygen levels.
The derived alveolar gas equation is based on the assumption of a steady state condition. The equation will only be valid if the assumptions upon which it was constructed remain true. Low FiO2 conditions could violate the steady state. Thus, some physicians and scientists suggest using the detailed form of the equation. In clinical practice, the full alveolar gas equation does not convey relevant increased accuracy and the abbreviated equation discussed above is sufficient in calculating the PO2 in alveoli.
Increasing altitude decreases the atmospheric pressure; thus, for any given FiO2, there is a lower PO2 in the atmosphere and a lower PAO2 in alveoli. For example, breathing 21% oxygen at sea level would result in an alveolar PO2 close to 100 mm Hg, while breathing the same % oxygen at Mount Everest (at an atmospheric pressure of 263 mm Hg) would result in alveolar PO2 close to 0 mm Hg.
As we ascend, barometric pressure goes down. This can lead to hypoxemia and trigger many physiologic changes.
Symptoms (in decreasing order of frequency) include:
A number of physiological changes occur which enable the body to function in a low oxygen environment. This process of gradual adjustment is known as acclimatization. This increases the frequency and depth of breathing, cardiac output, blood pressure, and production of erythropoietin and 2,3-diphosphoglycerate (2,3 DPG). Without proper acclimatization and/or supplemental oxygen, one can have high altitude cerebral edema, acute mountain sickness, and high altitude pulmonary edema.
On the other hand, increasing atmospheric pressure can have significant effects on the body by increasing the amount of dissolved oxygen in the blood. A hyperbaric oxygen chamber is used as a treatment for major carbon monoxide poisoning, decompression sickness, and non-healing ulcers.
Oxygen is used in the human body to perform oxidative phosphorylation and produce Adenosine Triphosphate (ATP), which is further used in enzymatic reactions as a primary form of energy. Oxygen has a high redox potential and is the last acceptor of electrons within the electron transport chain. Hypoxemic patients typically present with shortness of breath and dyspnea. If hypoxia is severe, they may develop severe lactic acidosis, cyanosis, syncope, and arrhythmias.
The alveolar gas equation helps us in calculating the alveolar and arterial PO2 gradient (A-a) difference.
Every 10% rise in the inspired fraction of oxygen increases the partial pressure of available oxygen in the alveoli by approximately 60 to 70 mm Hg.
If more than required FiO2 is given, it can lead to an increase in PO2 within the alveoli, and, if given for long periods of time, this can lead to lung injury. Higher levels of oxygen can be dangerous in end-stage chronic obstructive pulmonary disease patients, as their respiratory drive is dependent upon hypoxia (with a PO2 around 60 mm Hg).
Hyperoxygenation, by increasing the PO2 within the alveoli and plasma during the process of intubation or procedural conscious sedation, is very helpful and can be easily understood with the help of the alveolar gas equation. For example, at sea level with no additional supplemental oxygen and a normal physiological state, the PO2 inside the alveoli calculates at approximately 100 mm Hg.
For 100% oxygen:
PAO2 = (760 - 47) x 1 - (40 / 0.8)
(713) x 1 - 50 = 663 mm Hg
But, if a patient is given 100% oxygen in the same situation the PO2 can be as high as 663 mm Hg. In normal physiological conditions, this will give a clinician 8 to 9 minutes to successfully intubate before a patient’s partial pressure of oxygen falls below 60 mm Hg and desaturation on pulse oximetry becomes evident.
In pathological conditions where diffusion is impaired (congestive heart failure, pneumonia, alveolar hemorrhage), without pre-oxygenation, the clinician may have a few seconds to a few minutes before the patient will desaturate. In these severe pathological conditions, it is recommended that an experienced clinician attempt the intubation. In these conditions, bilevel positive airway pressure (BIPAP) can be used to pre-oxygenate and even hyperventilate the patient as long as they are hemodynamically stable, alert, awake, and able to protect the airway.
Carbon dioxide is the end product of carbohydrate metabolism. It is transported by red blood cells mostly bound to the hemoglobin to the lungs from peripheral tissues where it diffuses out and allowing hemoglobin to bind oxygen (Bohr and Haldane effects).
It is important to note that any increase in carbon dioxide must result in a decrease in the PO2. For example, if a patient is on room air with 0.21 FiO2 and is at sea level, as PaCO2 rises from 40 to 80 the PAO2 decreases from 100 to approximately 60 and patient will become hypoxemic. This emphasizes the importance of continuous capnography and pulse oximetry, especially during procedures where conscious sedation is used.
In hypoxic conditions, the normal response is hyperventilation and increasing the minute ventilation to exhale more carbon dioxide which decreases partial pressure of carbon dioxide and increases PO2 to some extent. For example, a decrease of 10 mm Hg PCO2 in alveoli will increase the PO2 by approximately 10 to 12 mm Hg, which can be very significant in acute and chronic disease processes. This is very important as an adaptation for survival.
The alveolar gas equation has some limitations, especially in low atmospheric pressures and low inspired FiO2. With the process of acclimatization, severe acidosis, and carbon monoxide poisoning the body’s physiology and pathophysiology are changed substantially, and the equation cannot be used reliably.