Skip to main content
SpringerLink
Log in

History of blood gas analysis. II. pH and acid-base balance measurements

  • Historical Review
  • Published:
Journal of Clinical Monitoring Aims and scope Submit manuscript

Abstract

Electrometric measurement of the hydrogen ion concentration was discovered by Wilhelm Ostwald in Leipzig about 1890 and described thermodynamically by his student Walther Nernst, using the van’t Hoff concept of osmotic pressure as a kind of gas pressure, and the Arrhenius concept of ionization of acids, both of which had been formalized in 1887. Hasselbalch, after adapting the pH nomenclature of SØrensen to the carbonic-acid mass equation of Henderson, made the first actual blood pH measurements (with a hydrogen electrode) and proposed that metabolic acid-base imbalance be quantified as the “reduced” pH of blood after equilibration to a carbon dioxide tension (PCO2) of 40 mm Hg. This good idea, coming 40 years before simple blood pH measurements at 37‡C became widely available, was never adopted. Instead, Van Slyke developed a concept of acid-base chemistry that depended on measuring plasma CO2 content with his manometric apparatus, a standard method until the 1960s, when it was displaced by the three-electrode method of blood gas analysis.

The 1952 polio epidemic in Copenhagen stimulated Astrup to develop a glass electrode in which pH could be measured in blood at 37‡C before and after equilibration with known PCO2. He introduced the interpolative measurement of PCO2 and bicarbonate level (later base excess) using only pH measurements and, with Siggaard-Andersen, developed clinical acid-base chemistry. Controversy arose when blood base excess was noted to be altered by acute changes in PCO2 and when abnormalities of base excess were called metabolic acidosis or alkalosis, even when they represented compensation for respiratory abnormalities in PCO2. In the 1970s it became clear that “in-vivo” or “extracellular fluid” base excess (measured at an average extracellular fluid hemoglobin concentration of 5 g) eliminated the error caused by acute changes in PCO2. Base excess is now almost universally used as the index of nonrespiratory acid-base imbalance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hasselbalch KA, Lundsgaard C: Elektrometrische Reaktionsbestimmung des Blutes bei Körpertemperatur. Biochem Z 1912;38:77–91

    Google Scholar 

  2. Warburg EJ: Studies on carbonic acid compounds and hydrogen ion activities in blood and salt solution—A contribution to the theory of the equation of L. J. Henderson and K. A. Hasselbalch. Biochem J 1922; 16:153–340

    PubMed  CAS  Google Scholar 

  3. Austin JH, Cullen GE: Hydrogen ion concentration of the blood in health and disease. Medicine 1925;4:275–343

    Article  Google Scholar 

  4. Hasselbalch KA: Die “reduzierte” und die “regulierte” Wasserstoffzahl des Blutes. Biochem Z 1916;74:56–62

    CAS  Google Scholar 

  5. Van Slyke DD. Neill JM: The determination of gases in blood and other solutions by vacuum extraction and manometric measurement. J Biol Chem 1924:61:523

    Google Scholar 

  6. Peters JP, Van Slyke DD: Quantitative clinical chemistry. Baltimore: Williams & Wilkins, 1932:

    Google Scholar 

  7. Van Slyke DD: Studies of acidosis. XVIII. The normal and abnormal variations in the acid base balance of the blood. J Biol Chem 1921;48: 153

    Google Scholar 

  8. Van Slyke DD, Wu H. McLean FC: Studies of gas and electrolyte equilibria in the blood. J Biol Chem 1923; 56:765–849

    Google Scholar 

  9. Stadie WC, Austin JH, Robinson HW: The effect of temperature on the acid-base protein equilibrium and its influence on the CO2 absorption curve of whole human blood, true and separated serum. J Biol Chem 1925; 66:901

    CAS  Google Scholar 

  10. Barcroft J. Bock AV, Hill AV, et al: On the hydrogen ion concentration and some related properties of normal human blood. J Physiol 1922;56:157–178

    PubMed  CAS  Google Scholar 

  11. Peters JP: Studies of the carbon dioxide absorption curve of human blood. III. A further discussion of the form of absorption curve plotted logarithmically, with a convenient type of interpolation chart. J Biol Chem 1923; 56:745

    CAS  Google Scholar 

  12. Eisenman AJ: A gasometric method for the determination of the pH of blood. J Biol Chem 1927;71:611

    CAS  Google Scholar 

  13. Douglas CG, Havard RE: The changes in the CO2 pressure and hydrogen ion concentration of the arterial blood of man which are associated with hyperpnea due to CO2. J Physiol 1932;74:471

    PubMed  CAS  Google Scholar 

  14. Rosenthal TB: The effect of temperature on the pH of blood and plasma in vitro. J Biol Chem 1948; 173:25–30

    PubMed  CAS  Google Scholar 

  15. Holaday DA: An improved method for multiple rapid determinations of arterial blood pH. J Lab Clin Med 1954;44:149–159

    PubMed  CAS  Google Scholar 

  16. Severinghaus JW, Stupfel M, Bradley AF: Accuracy of pH and PCO2 determinations. J Appl Physiol 1956;9:189–196

    PubMed  CAS  Google Scholar 

  17. Lassen HCA: Management of life threatening poliomyelitis, Copenhagen, 1952–56. (Translated from Danish by Hans Andersen.) Edinburgh: Livingstone, 1956:1–13

    Google Scholar 

  18. Ibsen B: From anaesthesia to anaesthesiology. Personal experiences in Copenhagen during the past 25 years. Acta Anaesthesiol Scand (Suppl) 1975;61:21–33

    Google Scholar 

  19. Astrup P: Om erkendelse af forstyrrelser i organismens syre/base stofskitfte. Ugeskr Laeg 1954; 116:758–771

    PubMed  CAS  Google Scholar 

  20. Siggaard-Andersen O: The Van Slyke equation. Scand J Clin Lab Invest 1977;37(Suppl 146): 15–20

    Article  CAS  Google Scholar 

  21. Woodbury JW: Body acid-base state and its regulation. In: Ruch TC and Patton HD, eds. Physiology and biophysics. Philadelphia: Saunders, 1974:487

    Google Scholar 

  22. Astrup P: A simple electrometric technique for the determination of carbon dioxide tension in blood and plasma, total content of carbon dioxide in plasma and bicarbonate content in “separated” plasma at a fixed carbon dioxide tension. Scand J Clin Lab Invest 1956;8:33–43

    Article  PubMed  CAS  Google Scholar 

  23. Astrup P, SchrØder S: Apparatus for anaerobic determination of pH in blood. Scand J Clin Lab Invest 1956;8:30

    Article  PubMed  CAS  Google Scholar 

  24. Brewin EG, Gould RP, Nashat FS, Neil E: An investigation of problems of acid-base equilibrium in hypothermia. Guy Hosp Rep 1955; 104:177

    CAS  Google Scholar 

  25. Stadie WC: An electron tube potentiometer for the determination of pH with the glass electrode. J Biol Chem 1929;83:477–492

    CAS  Google Scholar 

  26. JØrgensen K, Astrup P: Standard bicarbonate, its clinical significance, and a new method for its determination. Scand J Clin Lab Invest 1957;9:122–132

    Article  PubMed  Google Scholar 

  27. Woolmer RF, cd: A symposium on pH and blood gas measurement. London: J & A Churchill Ltd. 1959:1–196

    Google Scholar 

  28. Sanz MC: Ultramicro methods and standardization of equipment. Clin Chem 1957;3:406–419

    PubMed  CAS  Google Scholar 

  29. Siggaard-Andersen O, Engel K: A new acid-base nomogram. An improved method for the calculation of the relevant blood acid-base data. Scand J Clin Lab Invest 1960; 12:177–186

    Article  Google Scholar 

  30. Singer RB, Hastings AB: An improved clinical method for the estimation of disturbances of the acid-base balance of human blood. Medicine 1948;27:223

    Article  PubMed  CAS  Google Scholar 

  31. Astrup P: A new approach to acid-base metabolism. Clin Chem 1961;7:1–15

    PubMed  CAS  Google Scholar 

  32. Siggaard-Andersen O, Engel K, JØrgensen K, Astrup P: A micro method for determination of pH, carbon dioxide tension, base excess and standard bicarbonate in capillary blood. Scand J Clin Lab Invest 1960; 12:172–176

    Article  Google Scholar 

  33. Mellemgaard K, Astrup P: The quantitative determination of surplus amounts of acid or base in the human body. Scand J Clin Lab Invest 1960;12:187–199

    Article  Google Scholar 

  34. Siggaard-Andersen O: A graphic representation of changes of the acid-base status. Scand J Clin Lab Invest 1960;12:311–314

    Article  Google Scholar 

  35. Siggaard-Andersen O: The acid base status ot the blood. Scand J Clin Lab Invest 1963; 15(Suppl 70): 1–134

    PubMed  Google Scholar 

  36. Siggaard-Andersen O: Sampling and storing of blood for determination of acid-base status. Scand J Clin Lab Invest 1961;13:196–204

    Article  Google Scholar 

  37. Havard RE, Kerridge PT: An immediate acid change in shed blood. Biochem J 1928;23:600

    Google Scholar 

  38. Siggaard-Andersen O: Acute experimental acid base disturbances in dogs. An investigation of the acid base and electrolyte content of blood and urine. Scand J Clin Lab Invest 1963;66:1–20

    Google Scholar 

  39. Shaw LA, Messer AC: The transfer of bicarbonate between the blood and tissues caused by alterations of carbon dioxide concentration in the lungs. Amer J Physiol 1932; 100:122–136

    CAS  Google Scholar 

  40. Cunningham DIC, Lloyd BB, Michel CC: Acid base changes in the blood during hypercapnia and hypocapnia in normal man. Proc Physiol Soc 1961; 160:26–27

    Google Scholar 

  41. Brown EB Jr, Clancy RL: In vivo and in vitro CO2 blood buffer curves. J Appl Physiol 1965;20:885–889

    PubMed  CAS  Google Scholar 

  42. Severinghaus J: Acid-base balance nomogram—A Boston-Copenhagen détente. Anesthesiology 1976;45:539–541

    Article  PubMed  CAS  Google Scholar 

  43. Siggaard-Andersen O: The pH, log pCO2 blood acid-base nomogram revised. Scand J Clin Lab Invest 1962; 14:598–604

    Article  Google Scholar 

  44. Siggaard-Andersen O: Blood acid-base alignment nomogram. Scand J Clin Lab Invest 1963; 15:211–217

    Article  Google Scholar 

  45. Severinghaus JW: Blood gas calculator. J Appl Physiol 1966;21/1108–1116

    PubMed  CAS  Google Scholar 

  46. Visser BF, Maas AHJ: The pH-log PCO2 diagram of separated human blood plasma. Clin Chim Acta 1960;5:850–852

    Article  PubMed  CAS  Google Scholar 

  47. Maas AHJ, van Heist ANP: A comparison of the pH of arterial blood with arterialized blood from the earlobe with Astrup’s micro glass electrode. Clin Chim Acta 1961;6:31–33

    Article  PubMed  CAS  Google Scholar 

  48. Bunker J: Great trans-Atlantic acid-base debate. Anesthesiology 1965;25:591–594

    Google Scholar 

  49. Schwartz WB, Relman AS: A critique of the parameters used in evaluation of acid-base disorders. New Eng J Med 1963:268:1382–1388

    Article  PubMed  CAS  Google Scholar 

  50. Cohen JJ, Brackett NC Jr, Schwartz WB: The nature of the carbon dioxide titration curve in the normal dog. J Clin Invest 1964;43:777

    Article  PubMed  CAS  Google Scholar 

  51. Brackett NC Jr, Cohen JJ, Schwartz WB: Carbon dioxide titration curve of normal man. Effect of increasing degrees of acute hypercapnia on acid-base equilibrium. New Eng J Med 1965;272:6

    Article  PubMed  Google Scholar 

  52. Schwartz WB. Brackett NC Jr, Cohen JJ: The response of extracellular hydrogen ion concentration to graded degrees ot chronic hypercapnia: The physiologic limits ot the defense of pH. J Clin Invest 1965;44:291

    Article  PubMed  CAS  Google Scholar 

  53. Brackett NC Jr. Wingo CF, Muren O, Solano JT: Acidbase response to chronic hypercapnia in man. New Eng J Med 1969;280:124–130

    Article  PubMed  Google Scholar 

  54. Robin ED: Abnormalities ot acid-base regulation in chronic pulmonary disease, with special reference to hypercapnia and extracellular alkalosis. New Eng J Med 1963;268:917–922

    Article  PubMed  CAS  Google Scholar 

  55. Michel CC, Lloyd BB, Cunningham DJC: The in vivo carbon dioxide dissociation curve of true plasma. Resp Physiol 1966:1:121–137

    Article  CAS  Google Scholar 

  56. Prys-Roberts C, Kelman GR, Nunn JF: Determination of the in vivo carbon dioxide titration curve of anaesthetized man. Brit J Anaesth 1966;38:500–509

    Article  PubMed  CAS  Google Scholar 

  57. Siesjo BK, Messeter K: Factors determining intracellular pH. In: Siesjo BK, Sorensen SK, eds. Ion homeostasis of the brain. Copenhagen: Munksgaard, 1971:245–269

    Google Scholar 

  58. Engel K, Kildeberg P, Winters RW: Quantitative displacement of blood acid-base status in acute hypocapnia. Scand J Clin Lab Invest 1969;23:5–17

    Article  PubMed  CAS  Google Scholar 

  59. Roos A, Thomas LT: The in vitro and in vivo carbon dioxide dissociation curves ot true plasma. Anesthesiology 1967;28:1048–1063

    Article  PubMed  CAS  Google Scholar 

  60. Engel K, Dell RB, Rahill WJ, et al: Quantitative displacement of acid-base equilibrium in chronic respiratory acidosis. J Appl Physiol 1968;24:288–295

    PubMed  CAS  Google Scholar 

  61. Siggaard-Andersen O: An acid-base chart for arterial blood with normal and pathophysiological reference areas. Scand J Clin Lab Invest 1971;27:239–245

    Article  PubMed  CAS  Google Scholar 

  62. Levesque P, Severinghaus JW: The Boston-Copenhagen détente. Anesthesiology 1977;47:232–234

    Article  PubMed  CAS  Google Scholar 

  63. Severinghaus JW, Stupfel M, Bradley AF: Variations of pK′ with pH and temperature. J Appl Physiol 1956; 9:197–200

    PubMed  CAS  Google Scholar 

  64. Kelman GR, Coleman AJ, Nunn JF: Evaluation of a microtonometer used with a capillary glass pH electrode. J Appl Physiol 1966;21:1103–1107

    PubMed  CAS  Google Scholar 

  65. Kelman GR, Nunn JF: Nomograms for correction of blood PO2, PCO2, pH and base excess for time and temperature. J Appl Physiol 1966;21:1484

    PubMed  CAS  Google Scholar 

  66. Eisenman G, Bates R, Mattock G, Friedman SM: The glass electrode. New York: Interscience, 1966:1–318

    Google Scholar 

  67. Severinghaus JW: Design of capillary pH electrode incorporating an open liquid junction and reference electrode in a single unit. Scand J Clin Lab Invest 1965; 17:614–616

    Article  PubMed  CAS  Google Scholar 

  68. Hastings AB, Sendroy J: The effect of variations in ionic strength on the apparent first and second dissociation constants of carbonic acid. J Biol Chem 1925;65:445–455

    CAS  Google Scholar 

  69. Siggaard-Andersen O: Factors affecting the liquid junction potential in electrometric blood pH measurement. Scand J Clin Lab Invest 1961;13:205–211

    Article  Google Scholar 

  70. Siggaard-Andersen O: The first dissociation exponent of carbonic acid as a function of pH. Scand J Clin Lab Invest 1962; 14:587–597

    Article  CAS  Google Scholar 

  71. Austin WH. Littlefield SC: The difference in apparent pH of blood and buffer caused by raising the liquid junction from room temperature to 37.5‡C. J Lab Clin Med 1966; 67:516–519

    PubMed  CAS  Google Scholar 

  72. Maas AHJ, Rispens P, Siggaard-Andersen O, Zijlstra WG: On the reliability of the Henderson-Hasselbalch equation in routine clinical acid-base chemistry. Ann Clin Biochem 1984;21:26–39

    PubMed  CAS  Google Scholar 

  73. Semple SJG: Observed pH differences of blood and plasma with different bridge solutions. J Appl Physiol 1961; 16:576–577

    PubMed  CAS  Google Scholar 

  74. Peterson JI, Goldstein SR, Fitzgerald RV, Buckhold DK: Fiber optic pH probe for physiologic use. Anal Chem 1980:52:864–869

    Article  PubMed  CAS  Google Scholar 

  75. Nilsson E, Edwall G: Arterial pH monitoring with monocrystalline antimony sensors. A study of sensitivity for PO2 variations. Scand J Clin Lab Invest 1982;42:323–329

    Article  PubMed  CAS  Google Scholar 

  76. Nilsson E, Edwall G:Continuous intra-arterial pH monitoring using monocrystalline antimony as sensor. A study in non-heparinized dogs. Scand J Clin Lab Invest 1981; 41:333–338

    Article  PubMed  CAS  Google Scholar 

  77. Eisenman G: Glass electrodes for hydrogen and other cations. New York: Dekker, 1967:1–288

    Google Scholar 

  78. Durst RA, ed: Blood pH, gases and electrolytes. (NBS special publication 450). Washington: US Government Printing Office, 1976 (#SD C13.10:450)

    Google Scholar 

  79. Davenport HW: The ABC of acid-base chemistry. 6th ed. Chicago: University of Chicago Press, 1974:1–130

    Google Scholar 

  80. Henderson LJ: Blood as a physicochemical system. J Biol Chem 1921, 46:411

    CAS  Google Scholar 

  81. Filley GF: Acid-base and blood gas regulation. Philadelphia: Lea & Febiger, 1971:1–213

    Google Scholar 

  82. Saris NE: International Federation of Clinical Chemistry: Recommendations and Related Documents. New York: Walter de Gruyter, 1984:124–132

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesia, University of California Medical Center, San Francisco, CA

    John W. Severinghaus MD

  2. Department of Clinical Chemistry, Rigshospital, University of Copenhagen, Copenhagen, Denmark

    Poul B. Astrup Dr med (Professor Emeritus)

Authors
  1. John W. Severinghaus MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Poul B. Astrup Dr med
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Severinghaus, J.W., Astrup, P.B. History of blood gas analysis. II. pH and acid-base balance measurements. J Clin Monitor Comput 1, 259–277 (1985). https://doi.org/10.1007/BF02832819

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02832819

Key Words

Search

Navigation