Oxygenation of tissues is one of the most important processes that occur within the human body. Without proper oxygenation of tissues, metabolic processes cannot function efficiently, and cellular functions will falter. With such importance for the survival of an organism, it is understandable that the process of extracting oxygen from environmental air is tightly regulated physiologically. All gases follow chemical laws that when mixed, will each have a partial pressure equal to the hypothetical pressure when the same gas homogeneously occupies the same volume at the same temperature as the original mixture.[1]

The composition of environmental air is approximately 78% nitrogen, 21% oxygen, 1% argon, and trace percentages of carbon dioxide, neon, methane, helium, krypton, hydrogen, xenon, ozone, nitrogen dioxide, iodine, carbon monoxide, and ammonia. Therefore, at sea level where atmospheric pressure is known to be 760 mm Hg, the partial pressures of the various gases can be estimated to have partial pressures of approximately 593 mm Hg for nitrogen, 160 mm Hg for oxygen, and 7.6 mm Hg for argon. However, these partial pressures are not accurate reflections of the partial pressures available for diffusion within the alveoli of the lung. When air is inhaled through the upper airways, it is warmed and humidified by the pulmonary tract. The result of this process introduces the presence of significant levels of water vapor that then adjusts the partial pressures the other gases, including oxygen. It is not possible to collect gases directly from the alveoli. The alveolar gas equation is of great help in calculating and closely estimating the partial pressure of oxygen inside the alveoli. The alveolar gas equation is used to calculate alveolar oxygen partial pressure:

• PAO2 = (Patm - PH2O) FiO2 - PaCO2 / RQ

Where PAO2 is the partial pressure of oxygen in the alveoli, Patm is the atmospheric pressure at sea level equaling 760 mm Hg. PH2O is the partial pressure of water equal to approximately 45 mm Hg. FiO2 is the fraction of inspired oxygen. PaCO2 is the carbon dioxide partial pressure in alveoli, which in normal physiological conditions is approximately 40 to 45 mm Hg, and the RQ (respiratory quotient). FiO2 is directly related to the percent composition of oxygen in the inspired air. Without support at sea level, this is 21% or 0.21. However, each liter of supplemental oxygen in the inspired air increases this value by approximately 4% or 0.04. Therefore 2 liters of supplemented oxygen increases the FiO2 at sea level by 8% or 0.08 to 29% or 0.29. The value of RQ can vary depending upon the type of diet and metabolic state of the person. A standard value of 0.82 for the typical human diet. At sea level without supplemented inspired oxygenation, the alveolar oxygen partial pressure (PAO2) is:

• PAO2 = (760 - 47) 0.21 - 40 / 0.8 = 99.7 mm Hg

This alveolar partial pressure of oxygen then is the driving force for diffusion of oxygen across the alveolar membranes, through pulmonary capillary walls, and into the arteriolar blood flow and erythrocytes for transport throughout the body into peripheral tissues. The diffusion gradient from alveolar space into the capillary is quantified via the A-a gradient calculated as:

• A-a oxygen gradient = PAO2 - PaO2

PaO2 is measured using an arterial blood gas, and PAO2 is calculated as above. A larger gradient indicates pathology is hindering the transfer of oxygen into the capillary which has an impact on the available partial pressure of oxygen throughout the body. The necessary partial pressures of oxygen throughout tissues is variable depending on the metabolic demands of the tissues. The brain has been found to require a partial pressure of oxygen of at least 35 mm Hg below. Mental functions become impacted because aerobic metabolism of glucose for energy production cannot occur efficiently. The skin typically has a partial pressure spectrum based on the depth of skin layer from the surface. The superficial region of the skin at 5 to 10 micrometers depth is approximately 5.0 to 11 mm Hg partial pressure of oxygen. Dermal papillae at 45 to 65 micrometers depth typically have an 18 to 30 mm Hg partial pressure of oxygen, and at the subpapillary plexus of 100 to 120 micrometers depth, the partial pressure of oxygen is approximately 27 to 43 mm Hg. The intestines also have a variable partial pressure of oxygen with the serosal portion of small bowel being 53.0 to 71.0 mm Hg. Liver partial pressures of oxygen have been studied with somewhat variable results such that 2 separate groups were found to have median values of 42.04 mm Hg and 34.53 mm Hg. The kidneys make up another organ system which has a high oxygen requirement due to the high energy and subsequent metabolic demand involved in the active transport processes of the nephron reabsorption systems. As such, the medullary partial pressure of oxygen is 10 to 20 mm Hg, and the cortex requires 52 to 92 mm Hg. Muscular demand for oxygen is highly variable depending on the activity intensity and duration of the muscle. At baseline, muscular partial pressures of oxygen are 27 mm Hg to 31 mm Hg. Throughout the process of oxygen consumption by various tissues, the oxygen content of blood drops such that the 100 mm Hg in the arterial blood decreases to 40 mm Hg in venous blood.[2]

The primary measurement used to evaluate partial pressure of oxygen is arterial blood gas. This provides a direct measurement of the partial pressure of oxygen, the partial pressure of carbon dioxide, acidity (pH), oxyhemoglobin saturation, and bicarbonate concentration in arterial blood. All of these are useful for the evaluation and treatment of various disease states.

The partial pressure of oxygen is decreased through several disease processes. The primary processes include decreased inhaled oxygen, hypoventilation, diffusion limitations, and ventilation/perfusion mismatching (V/Q mismatch).

Changes in environmental pressure cause a change in the available oxygen for diffusion into the body. At sea level, the atmospheric pressure is 760 mm Hg. However, as elevation increases, atmospheric pressure decreases. For example, at the summit of Mt. Everest, the atmospheric pressure is as low as 260 mm Hg. When this pressure is used to calculate the alveolar partial pressure of oxygen in the environment, there is approximately 54.6 mm Hg oxygen available for diffusion. This is almost half of what is available at sea level.

Essentially, any pathology that decreases ventilation of the alveoli will lead to a hypoventilation defect. These can include:

• Central nervous system (CNS) depression or malformation from a neurologic deficit, Guillain-Barre, ALS, or drug overdose where the respiratory drive is decreased
• Obesity hypoventilation where the excess weight of the chest does not allow for proper inflation
• Muscular weakness
• Poor chest elasticity secondary to rib fracture or kyphoscoliosis

The result of hypoventilation on oxygenation is that air exchange between the alveolar space and the environment does not effectively occur. This decreases the partial pressure of oxygen in the alveolar space resulting in a lessened diffusion gradient which reduces the partial pressure of oxygen in the blood.

A ventilation-perfusion mismatch is as the name states, an imbalance between available ventilation and available arteriolar perfusion for oxygen to diffuse into circulation. Within a normal lung, there is variation throughout the tissue in response to oxygen and capillary demand. In the base of the lung, both perfusions are relatively greater than ventilation leading to a V/Q which is lesser than in the apices. Bronchoconstriction in lung tissue normally occurs to reduce ventilation to poorly perfused lung regions, and likewise, vasoconstriction in capillary arterioles normally occurs in poorly ventilated regions of the lung. Combined, these mechanisms work to balance the V/Q ratio so that the net effect is heterogeneous ventilation and perfusion with minimal pathological dead space or shunting.  In disease states such as pulmonary vascular diseases, interstitial disease, or obstructive lung disease the ratio of available lung ventilation to capillary perfusion is skewed netting hypoxic environments. This results in inefficient oxygen transfer into the capillary space with a resulting decreased partial pressure of oxygen in the blood.

A right-to-left shunt is an alternate pathological pathway of circulation that allows deoxygenated blood to bypass the lungs from the right side of the heart to the left side of the heart. Subsequently, oxygenation does not occur. Shunting is an example of extreme V/Q mismatching.[3][4][5]

Diffusion limitation exists when movement of oxygen from alveoli to pulmonary vasculature is impaired. This etiology is characterized by fibrosis of the lung and parenchymal destruction of alveoli leading to a decreased surface area of alveoli tissue. Often diffusion abnormalities are coexisting with V/Q mismatching and are most prevalent under exercise conditions. During rest blood flow through the lung arterioles is slow enough to allow for proper diffusion regardless of an increased A-a gradient. However, under exercise conditions, cardiac output increases. When this occurs, there is less time for oxygenation to occur in the lung which leads to transient hypoxia. Examples of limited diffusion disease include lung fibrosis and chronic obstructive pulmonary disease. The result is a normal partial pressure of oxygen in the alveolar space, but a low partial pressure of oxygen in the arterial space.[6][7][8]