Introduction

Humans are highly aerobic organisms consuming oxygen per metabolic demand.[1] In aerobic respiration, oxygen, and pyruvate produce adenosine triphosphate (ATP), producing energy for the whole body.[2] To maintain homeostasis, there needs to be a gradient of pressure within the tissues that pushes oxygen by diffusion from the membranes into the tissues.[3] Many factors influence the amount of dissolved oxygen present within the cells and tissues, such as

• Barometric pressure (BP)
• Climatological conditions (temperature, latitude, relative humidity, altitude)
• Physiological, pathological, and physical-chemical processes [4]

Oxygenation of tissues is 1 of the essential processes in the human body. Without proper oxygenation of tissues, metabolic processes cannot function efficiently, and cellular functions 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, each has 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.[5]

Function

The composition of environmental air is approximately 78% nitrogen, 21% oxygen, 1% argon, and trace percentages of other gases, such as carbon dioxide, neon, methane, helium, krypton, hydrogen, xenon, ozone, nitrogen dioxide, iodine, carbon monoxide, and ammonia. Therefore, at sea level, where atmospheric pressure is 760 mmHg, the partial pressures of the various gases can be estimated to have partial pressures of approximately 593 mmHg for nitrogen, 160 mmHg for oxygen, and 7.6 mmHg for argon.

However, these partial pressures do not accurately reflect the partial pressures available for diffusion within the lung's alveoli. When air is inhaled through the upper airways, it is warmed and humidified by the pulmonary tract. This process introduces water vapors that adjust the partial pressures of all gases, including oxygen. Therefore, partial pressure of oxygen within the upper airway is taken as inspired PO (PiO). Water vapor pressure is static at 47 mmHg at body temperature and significantly depends on temperature.[6]

It is not possible to collect gases directly from the alveoli. However, 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 = (P_atm - PH₂O) FiO₂ - PACO₂ / RQ

While PAO₂ is the partial pressure of oxygen in the alveoli, P_atm is the atmospheric pressure at sea level equaling 760 mm Hg. PH₂O is the partial pressure of water equal to approximately 45 mmHg. FiO₂ is the fraction of inspired oxygen. PCO₂ is the partial pressure of carbon dioxide in the arteries, about 40 to 45 mmHg in normal physiological conditions, 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 increase the FiO₂ at sea level by 8% or 0.08 to 29% or 0.29. The value of RQ can vary depending on 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 is the driving force for the 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 arterial blood gas, and PAO₂ is calculated above. A larger gradient indicates an underlying pathology hindering the transfer of oxygen into the capillary, which impacts the available partial pressure of oxygen throughout the body. The necessary partial pressure of oxygen throughout tissues is variable depending on the metabolic demands of the tissues. This diffusion gradient is the tissue partial pressure of oxygen (PtO) and varies with capillary density, oxygen consumption, metabolic rate, and blood flow.[7] The brain has been found to require a partial pressure of oxygen between 30 and 48 mmHg.[7][3]

Mental functions become impacted because the aerobic metabolism of glucose for energy production cannot occur efficiently. The skin typically has a partial pressure spectrum based on the depth of the skin layer from the surface. The superficial region of the skin at 5 to 10 micrometers depth is approximately 5.0 to 11 mmHg partial pressure of oxygen. Dermal papillae at 45 to 65 micrometers depth typically have an 18 to 30 mmHg partial pressure of oxygen. At the subpapillary plexus of 100 to 120 micrometers depth, the partial pressure of oxygen is approximately 27 to 43 mmHg.

The intestines also have a variable partial pressure of oxygen, with the serosal portion of the small bowel being 53.0 to 71.0 mmHg. The liver's partial pressure of oxygen has been studied with somewhat variable results such that 2 groups were found to have median values of 42.04 mmHg and 34.53 mmHg. The kidneys make up another organ system with 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 mmHg, and the cortex requires 52 to 92 mmHg. Muscular demand for oxygen is highly variable depending on the activity intensity and duration of the muscle. At baseline, muscular partial pressures of oxygen range between 27 mmHg and 31 mmHg.[8] Throughout the process of oxygen consumption by various tissues, the oxygen content of blood drops such that the 100 mmHg in the arterial blood decreases to 40 mmHg in venous blood.[9]

Clinical Significance

The primary measurement used to evaluate the 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 evaluating and treating various disease states.

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

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

Essentially, any pathology that decreases ventilation of the alveoli leads 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, reducing the partial pressure of oxygen in the blood.

As the name states, a ventilation-perfusion mismatch is an imbalance between available ventilation and 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 reduces ventilation to poorly perfused lung regions; likewise, vasoconstriction in capillary arterioles normally occurs in poorly ventilated lung regions. Combined, these mechanisms 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. This results in inefficient oxygen transfer into the capillary space, resulting in 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 to the left side of the heart. Subsequently, oxygenation does not occur. Shunting is an example of extreme V/Q mismatching.[10][11][12]

Diffusion limitation exists when the movement of oxygen from alveoli to pulmonary vasculature is impaired. This etiology is characterized by lung fibrosis and parenchymal destruction of alveoli, leading to a decreased surface area of alveolar tissue. Often, diffusion abnormalities coexist with V/Q mismatching and are most prevalent under exercise conditions. During rest, blood flow through the lung arterioles is slow enough to allow 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.[13][14][15]

The significance of understanding the partial pressure of oxygen and its gradient among healthcare providers is immense. Understanding the functioning of the pressure gradient and how an adequate amount of oxygen is delivered to tissues is associated with a whole spectrum of clinical uses. Some important results are observed from athletes' performance, forecasting mortality due to prevalent diseases, treatment effectiveness in ulcers, wound healing evaluation, burns, cancer, or cerebral and cardiovascular diseases.[16][17][18][19][20]

In this sense, this activity discusses the physiological mechanisms, the techniques for measuring, and the pressure values observed in different organ systems, from the atmosphere to the mitochondrial pathways. Tissue partial pressure of oxygen shows a balance between tissue oxygen consumption rate and arterial blood flow. As a result of technical restrictions and confounding factors such as inflammation, anesthesia, restraint, and hypoxia, an evaluation of partial pressure of oxygen amidst normal conditions is excessively difficult. However, clinical and in vivo data help us understand the mechanisms regulating the partial pressure of oxygen within the human body.

Enhancing Healthcare Team Outcomes

All interprofessional healthcare team members, particularly those dealing with patients with respiratory or other circulatory issues that impair oxygen delivery, should understand the concept and physiological implications of partial pressure of oxygen. This includes clinicians, specialists, nurses, and pulmonary therapists. Knowing how to use this value can aid in diagnosis and help shape the treatment and management strategy for these patients, resulting in better outcomes.

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Disclosure: Sandeep Sharma declares no relevant financial relationships with ineligible companies.

Disclosure: Muhammad Hashmi declares no relevant financial relationships with ineligible companies.