Our understanding of acid-base balance depends on numerous underlying inventions, discoveries and theories. Blood gas analysis is used frequently partly because it is now convenient, and partly because of the growth in our knowledge and understanding of acid base physiology.
Interest in acid base balance stems from its physiologic importance, from fascination in a subject which has exercised and challenged scientific interest during the last century and, regrettably, from the requirement to set and pass examinations
The history has been presented as a book, The History of Blood Gases and Bases by Poul Astrup and John Severinghaus as well as summarized in their series of Review-Essays in the Journal of Clinical Monitoring (1985, 1986). Some of the critical events and participants that they mention are summarized in the historical summary below which emphasizes several points:
- The time taken for ideas and equipment to penetrate.
- The names of the prominent investigators.
- The approaches to measuring metabolic disturbances.
- The controversy surrounding the introduction of "base excess".
Principal Historical Events
- 1660: Boyle
- Reported that Pressure in a gas is inversely proportional to its volume - which became known as "Boyle's Law." Boyle actually gave credit to for this finding to Robert Hooke. The French have a claimant, Edme Mariotte, who published work on this topic in 1676 and so the full name of this law may be: The Boyle-Marriotte Law
- 1749: Benjamin Franklin
- Submitted a summary of his experiments in which he called "vitreous" charges "positive" which later necessitated the labeling of excess electrons with the adjective "negative".
- 1801: Dalton
- Proposed law of partial pressures.
- 1802: Henry
- "Dissolved gas proportional to partial pressure."
- 1808: Gay-Lussac
- "Pressure proportional to 'absolute' temperature". Law of combining volumes.
- 1811: Avagadro
- Equal volumes of all gases at the same temperature and pressure contain equal numbers of molecules
- 1833: Faraday
- Coined terminology (ion, anion, anode, etc.) and established laws of electrolysis.
- 1848: Lord Kelvin
- Combined known gas laws to permit calculation of the universal gas constant, R, in:
PV=nRT (P = pressure, V = volume, n = number of moles, and T = temperature).
- 1857: Clausius
- Concluded that ions already exist in solutions.
- 1887: Van't Hoff
- Linked the "gas laws" to the behavior of osmotic pressure in solutions.
- 1887: Arrhenius
- Proved that dissolved salts and acids are ionized, thus introducing the concept of the Hydrogen ion - H+.
- 1887: Ostwald
- Made first electrical measurement of hydrogen ion concentration.
- 1889: Nernst
- Derived equation which related change in voltage to the universal gas constant (R), the absolute temperature (T), the valence (n), the faraday (F) and the activity (a):
E = Eo + [RT/nF] log(a/ao ). (note: RT/nF = 61.5 mV at 37o C)
- 1889: Nernst
- Also recommended selecting salts with ions having similar diffusion rates to avoid error voltages at liquid junctions.
- 1905: Bjerrum
- Adopted Nernst's recommendation; introduced now standard potassium chloride salt bridge.
- 1906: Cremer
- Discovered that a difference in acidity can cause a potential difference across the glass membrane.
- 1908: Henderson of the "Henderson Equation"
- Discovered buffering power of CO2 and applied law of mass action:
K = [H+] [HCO3-] / [dCO2] (where dCO2 = dissolved CO2)
- Sorensen (1909)
- Suggested the pH terminology. Also developed the hydrogen electrode for biologic use.
- 1916: Hasselbalch
- Used Sorensen's terminology for Henderson's equation in logarithmic form:
pH = pK + log(HCO3-/dCO2)
- 1916: Hasselbalch
- Proposed measuring metabolic acidosis using "Standard pH" at 38oC with PCO2 = 40 mm Hg (analogous to the 'standard' bicarbonate later introduced by Jorgensen and Astrup).
- 1921: Van Slyke
- Published acid-base diagram using, as axes, log[H+]:log(PCO2) the forerunner of the in-vivo Siggaard- Andersen diagram (1971).
- 1923: Brønsted and Lowry
- Independently, Johannes Nicolaus Brønsted and Martin Lowry characterized acids and bases as donors or acceptors of protons (hydrogen ions). They also stated that when an acid ionizes in water, the "free" hydrogen ion is often attached to H2O to make H3O+.
- 1924: Van Slyke
- Originated manometric Van Slyke apparatus to measure gas quantities released from blood.
- 1927: Eisenman
- Derived pH by interpolation on a graph using log(CO2 content):log(PCO2) axes. Measurements of CO2 content were made using Van Slyke measurement at known PCO2.
- 1929: MacInnes and Dole
- Perfected glass composition for pH electrodes (later known as 015 pH glass - Corning).
- 1933: MacInnes and Belcher
- Designed the first commercial electrode to measure blood pH.
- 1952: Poul Astrup
- Encountered the need to measure PCO2 in his clinical laboratory during the Copenhagen polio epidemic, and derived PCO2 by interpolation on a graph of log (PCO2): pH. Measurements of pH were made at known PCO2 levels.
- 1954: Stow
- Covered pH and reference electrode with rubber to make a practical PCO2 electrode, later modified and improved by Severinghaus.
- 1956: Poul Astrup
- Designed practical thermostatically controlled glass electrode in a CO2 equilibration chamber.
- 1957: Jorgensen and Astrup
- Introduced "Standard Bicarbonate" (the bicarbonate level at PCO2 = 40 mmHg) as the "best available measure of non-respiratory disturbances".
- 1958: Astrup and Siggard-Andersen
- Introduced the capillary microelectrode and the concept "Base-Excess" as a measure of treatment required to correct metabolic disturbances. The "in-vitro" base excess was dependent on the hemoglobin level - subsequently a source of criticism and debate.
- 1958: Severinghaus and Bradley
- Demonstrated blood-gas apparatus which contained both PCO2 and PO2 electrodes.
- 1962: Siggaard-Andersen
- Published acid-base nomogram using log(PCO2):pH axes for calculating, by interpolation, the PCO2, the bicarbonate, the standard bicarbonate and the base-excess. The technique required pH to be measured at known PCO2 levels.
- 1963: Siggaard-Andersen
- Published alignment nomogram.
- 1963: Schwartz and Relman
- Critically reviewed the concept "base-excess" and proposed the use of linear equations to characterize acid-base syndromes. By this means they avoided describing the adaptation to chronic hypercapnia as "metabolic alkalosis" but, rather, they regarded the patient as being compensated to chronic hypercapnia if he fitted their equation.
- 1966: Severinghaus
- Developed blood-gas slide rule.
- 1971: Siggaard-Andersen
- Published In-Vivo Diagram (see Van Slyke 1921)
- 1974: Grogono, Byles, and Hawke
- Published a simple In-Vivo Diagram based on the Siggaard-Andersen nomogram but employing for the axes the two clinical components, metabolic acidosis and respiratory acidosis.
- 1983: Stewart
- In his book in 1981 and paper in 1983 Stewart introduced his concept of employing Strong Ion Difference (SID) as an alternative technique for assessing acid-base disturbances. It has been one more source of acid-base controversy. In conjunction with added complexity and a lack of confirmed benefit, this has prevented it from from receiving widespread acceptance.
- 1986: Astrup and Severinghaus
- Published the wonderful book: The History of Blood Gases, Acids, and Bases, from which I have drawn nearly all of the historical information.
- 1997: Sahlin et al
- Described a method of measuring intracellular pH (pHi) in muscle of resting volunteers. They calculated that pHi = 7.0 +/- 0.06; and intracellular bicarbonate = 10.2 +/- 1.2 mMol/L;
- 1997: Schlichtig, Grogono, and Severinghaus
- Reviewed the literature and devised new, accurate regressions between Standard Base Excess (SBE) and PCO2 which characterized the classical acid-base disturbances; they also introduced a revised In-vivo Acid Base Diagram. See: Human PaCO2 and Standard Base Excess Compensation., and Acid-base quantitation in Physiology and Medicine which are the sources for the regression equations and the new diagrams used in this website.
Alan W. Grogono
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