Introduction and history of blood gases
The term “blood gas” refers to the parameters pH, p CO 2 , and p O 2 measured in blood. Note that the little “p” in pH stands for negative log, while the italicized p in p CO 2 and p O 2 stands for the partial pressure of each of these gases. In addition to pH, p CO 2 , and p O 2 , modern “blood gas analyzers” may also measure the hemoglobin fractions, electrolytes, and metabolites such as sodium, potassium, ionized calcium, chloride, bicarbonate, glucose, and lactate. Some analyzers also include measurements of creatinine, urea, and ionized magnesium.
The history of blood gases and oximetry has perhaps the oldest, best documented, and, to some of us, the most interesting history of developments in laboratory tests. The history includes many notable figures, including Joseph Priestley, who became fascinated observing the large volume of gas produced in making beer and then went on to isolate 10 different gases, including oxygen in the late 1700s. Around that time, the eccentric and exceedingly wealthy (by an unexpected inheritance) Henry Cavendish, once described as “the richest of all learned men, and probably also the most learned of all the rich , ” discovered hydrogen, characterized carbon dioxide, and was the first person to accurately analyze atmospheric air. The early history of blood gases even includes Benjamin Franklin, a colleague of many scientists including Priestley and a founding father of the United States of America. To paraphrase Alan Grogono: “In addition to publishing newspapers, drafting constitutions, serving as postmaster general, flying kites in thunderstorms, discovering the Gulf Stream, and maintaining friendships with French ladies, Benjamin Franklin found time to make an unfortunate guess about calling “vitreous” charges “positive.” This decision later led to assigning a “negative” charge to electrons and a “positive” charge to hydrogen ions ( ) .
Several distinguished scientists have contributed to the definition of an acid. In the late 1800s, Arrhenius defined acids as hydrogen salts. In the early 1900s, Lawrence Henderson and Karl Hasselbalch sequentially characterized the buffering relationship between an acid and base thereby creating the eponymous Henderson–Hasselbalch equation, but who never actually knew each other. Brønsted and Lowry simultaneously, but separately, defined acids as substances that could donate a hydrogen ion, and Gilbert Lewis later described an acid as any compound that could accept a pair of electrons to form a covalent bond.
Donald Van Slyke embraced the idea that acid–base status was partly determined by electrolytes, an idea that was expanded by Peter Stewart into the very complex Strong-Ion-Difference explanation of acid–base balance ( ) . Importantly, Van Slyke is credited with expanding chemical analyses into the hospital and is considered a founder of “clinical chemistry.” One of his most notable discoveries was the gasometric method, which measured released O 2 gas and consequentially the oxygen saturation in the blood. Before and during World War II, Kurt Kramer, J.R. Squires, and Glen Millikan made significant advancements in oximetry, which led to its integrated use with oxygen-delivery systems enabling safer high-altitude military flights. These developments eventually led Takuo Aoyagi to the discovery of pulse oximetry in the 1970s, which allows for the separation of the arteries absorption of hemoglobin from the absorption of the tissue using the pulsatile nature of the arterial absorption signal.
The prototype electrode for measuring the partial pressure of oxygen ( p O 2 ) was developed in 1954 by Leland Clark, using polyethylene film and other materials that cost less than a dollar. Also in 1954, Richard Stowe covered a pH electrode with a rubber finger covering to develop a prototype of today’s partial pressure of carbon dioxide ( p CO 2 ) electrodes. These stories and many others that led to the development of the blood-gas analyzer were documented in a book by Astrup and Severinghaus ( ) .
The methodology for measuring clinical blood gases has evolved dramatically from mostly large laboratory-dedicated analyzers to hybrid analyzers adaptable to both laboratory and near-patient settings. There has also been a huge growth in the use of portable hand-held analyzers that are suited for smaller laboratories and near-patient use in hospitals, clinics, or remote locations. Blood gas testing is widely used as a tool for diagnosing disorders and evaluating the efficacy of therapeutic interventions.
Explanations of blood gas, acid–base, and cooximetry terms
pH . pH is an index of the acidity or alkalinity of the blood. Normal arterial pH is 7.35–7.45. A pH <7.35 indicates an acid state, and a pH >7.45 indicates an alkaline state. Acidemia refers to the condition of the blood being too acidic, and acidosis refers to the metabolic or respiratory process within the patient that causes acidemia. The adjective for the process is acidotic. Similar terms are used for the alkaline state: alkalemia, alkalosis, and alkalotic. Because all enzymes and physiological processes may be affected by pH, pH is normally regulated within a very tight physiologic range, especially within an individual, but also for reference intervals (see Table 1.1 ).
|Test||Age category||Ref ( )||Duke medical center||Ref ( )||Ref ( , )|
|p CO2 mmHg||1–2 h||32–45|
|p CO 2 mmHg||20–76 years||39–55||35–45||41–51||35–45||32–45 (F) |
|p O 2 mmHg||1–2 h||65–96|
|p O 2 mmHg||20–39 years||83–115|
|p O 2 mmHg||40–76 years||70–110|
|p O 2 mmHg||2 days–60 years||30–55||75–108||30–40||80–100|
|sO 2 (%)||∼75||>95|
|Base excess||−3.0 to +3.0||−3.0 to +2.8|
|HCO 3 mmol/L |
Total CO 2
|Anion gap mmol/L||5–11|
p CO 2 . p CO 2 is a measure of the tension or pressure of carbon dioxide dissolved in the blood. The p CO 2 of blood represents the balance between cellular production and diffusion of CO 2 into the blood and ventilatory removal of CO 2 from blood. A normal, steady p CO 2 indicates that the lungs are removing CO 2 from blood at about the same rate as CO 2 produced in the tissues is diffusing into the blood. A change in p CO 2 indicates an alteration in this balance. CO 2 is an acidic gas that is largely controlled by our rate and depth of breathing or ventilation, which changes to match the rate of metabolic production of CO 2 . p CO 2 is classified as the respiratory or ventilatory component of acid–base balance.
p O 2 . p O 2 is a measure of the tension or pressure of oxygen dissolved in the blood. The p O 2 of arterial blood is primarily related to the ability of oxygen to enter the lungs and diffuse across the alveoli into the blood. As shown in Fig. 1.1 , there is a continual gradient of p O 2 from atmospheric air (150 mmHg) to the alveoli (∼110 mmHg), to arterial blood (∼100 mmHg), capillaries (∼60 mmHg) and venous blood (∼40 mmHg), and finally to the mitochondria in cells with the lowest p O 2 of ∼8–12 mmHg. These gradients drive the movement, binding, and release of oxygen among these systems.
Common causes of a decreased arterial p O 2 are listed below, with further details presented in Chapter 4:
Hypoventilation: Alveolar ventilation is low relative to O 2 uptake and CO 2 production, which leads to decreased alveolar p O 2 and increased alveolar p CO 2 . Example: severe obstructive lung disease.
Low oxygen environment: Partial pressure of oxygen in inspired air is less than 160 mmHg. This is most commonly seen at high altitudes.
Ventilation/perfusion (V/Q) mismatch: Areas within the lung are receiving inspired air, but the perfusion to that portion of the lung is limited. Example: Pulmonary embolism, where a clot lodges in a pulmonary artery to limit blood flow to an otherwise functioning lung unit.
Shunt: A portion of the blood travels from the venous system to the arterial system without contact with a functioning alveolar unit. Example: Lung disease where blood flows through portions of the lung that are unventilated due to complete airway obstruction, atelectasis, or filling with fluid or cells.
Diffusion impairment: Oxygen is unable to efficiently transfer across the blood-gas barrier of the alveoli. Examples: Thickening of the blood-gas barrier due to fibrosis, edema, or inflammatory cell infiltration.
Bicarbonate . Although the bicarbonate ion (HCO 3 – ) can now be measured directly, some blood-gas analyzers calculate [HCO 3 – ] with the Henderson–Hasselbalch equation from measurements of the pH and p CO 2 . Bicarbonate is an indicator of the buffering capacity of blood and is classified as the metabolic component of acid–base balance.
Base Excess . Base excess (BE) is a calculated term that describes the amount of bicarbonate relative to p CO 2 . Standard BE reflects only the metabolic component of acid–base disturbances. It is based on the titratable fluid volume throughout the body (both extravascular and vascular (blood)) and also includes the contribution of Hb for acid–base disturbances.
The BE concept has a long history with some spirited controversy that is reviewed by Johan Kofstad, a professional colleague and most gracious friend who I met in Oslo on my first trip to Europe in 1983 ( ) . Base excess was conceived by Astrup in the 1950s and refined with equations and nomograms by Siggaard-Andersen in 1960. In 1977, attempting to resolve controversies about BE between the Americans and Denmark, Severinghaus proposed a modified nomogram. However, the different beliefs related to whether BE should be calculated in blood or extracellular fluid remain unreconciled to this day.
Equations for calculating extracellular base excess (BE ECF ) from pH and either HCO 3 (mmol/L) or p CO 2 (mmHg) appear to be different but are eerily similar. Here are two equations used for calculating BE ( , ) :
The “normal” reference interval for BE is −3 to +3 mmol/L. Comparison of the calculated BE to the reference range for BE may help determine whether an acid/base disturbance is a respiratory, metabolic, or mixed metabolic/respiratory problem. A base excess value exceeding +3 indicates metabolic alkalosis such that the patient requires increased amounts of acid to return the blood pH to neutral if p CO 2 is normal. A base excess below −3 indicates metabolic acidosis and excess acid needs to be removed from the blood to return the pH back to neutral if p CO 2 is normal. My personal opinion is that the BE calculation adds little to the simple interpretation of the difference of the measured bicarbonate −24, especially for pH from 7.3 to 7.5, as noted below and in Table 1.2 .
|pH||HCO 3||p CO 2||BE||HCO 3 − 24|
When the value of the BE is a negative number, it is frequently referred to as a base deficit (BD). The BD is often used to guide resuscitation in patients suffering from shock where hypoperfusion leads to inadequate delivery of oxygen to the tissue resulting in metabolic acidosis ( ) . As the patient is successfully resuscitated and oxygen delivery restored, the BD will begin to normalize. In patients who have undergone acute physical trauma, the BD has a significant prognostic value ( ) .
Table 1.2 shows that the relationship between BE and the simple difference of (measured bicarbonate—24 mmol/L) is usually 2 mmol/L or less, especially for pH from 7.3 to 7.5 as noted earlier. We leave it to each reader to determine the clinical importance of calculating BE versus the use of the bicarbonate concentration.
The anion gap (AG) is a calculated term for the difference between the commonly measured cations (Na + and sometimes K + ) and the commonly measured anions (Cl − and HCO 3 − ). Therefore, it represents the unmeasured anions such as negatively charged proteins (particularly albumin) and lactate, phosphates, sulfates, urates, and ketones produced by the body. Exogenous toxins and drugs, including methanol, salicylate, and ethylene glycol (and its metabolites), also contribute to the anion gap when present. The AG is calculated as follows:
If K + is included in the calculation, the formula is as follows: