Journal of Clinical Monitoring

, Volume 1, Issue 4, pp 259–277 | Cite as

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

  • John W. Severinghaus
  • Poul B. Astrup
Historical Review

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.

Key Words

Acid-base equilibrium: base excess buffer base standard bicarbonate Measurement techniques: electrodes, pH tonometry Van Slyke 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hasselbalch KA, Lundsgaard C: Elektrometrische Reaktionsbestimmung des Blutes bei Körpertemperatur. Biochem Z 1912;38:77–91Google Scholar
  2. 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; 16:153–340PubMedGoogle Scholar
  3. 3.
    Austin JH, Cullen GE: Hydrogen ion concentration of the blood in health and disease. Medicine 1925;4:275–343CrossRefGoogle Scholar
  4. 4.
    Hasselbalch KA: Die “reduzierte” und die “regulierte” Wasserstoffzahl des Blutes. Biochem Z 1916;74:56–62Google Scholar
  5. 5.
    Van Slyke DD. Neill JM: The determination of gases in blood and other solutions by vacuum extraction and manometric measurement. J Biol Chem 1924:61:523Google Scholar
  6. 6.
    Peters JP, Van Slyke DD: Quantitative clinical chemistry. Baltimore: Williams & Wilkins, 1932:Google Scholar
  7. 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: 153Google Scholar
  8. 8.
    Van Slyke DD, Wu H. McLean FC: Studies of gas and electrolyte equilibria in the blood. J Biol Chem 1923; 56:765–849Google Scholar
  9. 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; 66:901Google Scholar
  10. 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;56:157–178PubMedGoogle Scholar
  11. 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; 56:745Google Scholar
  12. 12.
    Eisenman AJ: A gasometric method for the determination of the pH of blood. J Biol Chem 1927;71:611Google Scholar
  13. 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;74:471PubMedGoogle Scholar
  14. 14.
    Rosenthal TB: The effect of temperature on the pH of blood and plasma in vitro. J Biol Chem 1948; 173:25–30PubMedGoogle Scholar
  15. 15.
    Holaday DA: An improved method for multiple rapid determinations of arterial blood pH. J Lab Clin Med 1954;44:149–159PubMedGoogle Scholar
  16. 16.
    Severinghaus JW, Stupfel M, Bradley AF: Accuracy of pH and PCO2 determinations. J Appl Physiol 1956;9:189–196PubMedGoogle Scholar
  17. 17.
    Lassen HCA: Management of life threatening poliomyelitis, Copenhagen, 1952–56. (Translated from Danish by Hans Andersen.) Edinburgh: Livingstone, 1956:1–13Google Scholar
  18. 18.
    Ibsen B: From anaesthesia to anaesthesiology. Personal experiences in Copenhagen during the past 25 years. Acta Anaesthesiol Scand (Suppl) 1975;61:21–33Google Scholar
  19. 19.
    Astrup P: Om erkendelse af forstyrrelser i organismens syre/base stofskitfte. Ugeskr Laeg 1954; 116:758–771PubMedGoogle Scholar
  20. 20.
    Siggaard-Andersen O: The Van Slyke equation. Scand J Clin Lab Invest 1977;37(Suppl 146): 15–20CrossRefGoogle Scholar
  21. 21.
    Woodbury JW: Body acid-base state and its regulation. In: Ruch TC and Patton HD, eds. Physiology and biophysics. Philadelphia: Saunders, 1974:487Google Scholar
  22. 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;8:33–43PubMedCrossRefGoogle Scholar
  23. 23.
    Astrup P, SchrØder S: Apparatus for anaerobic determination of pH in blood. Scand J Clin Lab Invest 1956;8:30PubMedCrossRefGoogle Scholar
  24. 24.
    Brewin EG, Gould RP, Nashat FS, Neil E: An investigation of problems of acid-base equilibrium in hypothermia. Guy Hosp Rep 1955; 104:177Google Scholar
  25. 25.
    Stadie WC: An electron tube potentiometer for the determination of pH with the glass electrode. J Biol Chem 1929;83:477–492Google Scholar
  26. 26.
    JØrgensen K, Astrup P: Standard bicarbonate, its clinical significance, and a new method for its determination. Scand J Clin Lab Invest 1957;9:122–132PubMedCrossRefGoogle Scholar
  27. 27.
    Woolmer RF, cd: A symposium on pH and blood gas measurement. London: J & A Churchill Ltd. 1959:1–196Google Scholar
  28. 28.
    Sanz MC: Ultramicro methods and standardization of equipment. Clin Chem 1957;3:406–419PubMedGoogle Scholar
  29. 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; 12:177–186CrossRefGoogle Scholar
  30. 30.
    Singer RB, Hastings AB: An improved clinical method for the estimation of disturbances of the acid-base balance of human blood. Medicine 1948;27:223PubMedCrossRefGoogle Scholar
  31. 31.
    Astrup P: A new approach to acid-base metabolism. Clin Chem 1961;7:1–15PubMedGoogle Scholar
  32. 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; 12:172–176CrossRefGoogle Scholar
  33. 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;12:187–199CrossRefGoogle Scholar
  34. 34.
    Siggaard-Andersen O: A graphic representation of changes of the acid-base status. Scand J Clin Lab Invest 1960;12:311–314CrossRefGoogle Scholar
  35. 35.
    Siggaard-Andersen O: The acid base status ot the blood. Scand J Clin Lab Invest 1963; 15(Suppl 70): 1–134PubMedGoogle Scholar
  36. 36.
    Siggaard-Andersen O: Sampling and storing of blood for determination of acid-base status. Scand J Clin Lab Invest 1961;13:196–204CrossRefGoogle Scholar
  37. 37.
    Havard RE, Kerridge PT: An immediate acid change in shed blood. Biochem J 1928;23:600Google Scholar
  38. 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;66:1–20Google Scholar
  39. 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; 100:122–136Google Scholar
  40. 40.
    Cunningham DIC, Lloyd BB, Michel CC: Acid base changes in the blood during hypercapnia and hypocapnia in normal man. Proc Physiol Soc 1961; 160:26–27Google Scholar
  41. 41.
    Brown EB Jr, Clancy RL: In vivo and in vitro CO2 blood buffer curves. J Appl Physiol 1965;20:885–889PubMedGoogle Scholar
  42. 42.
    Severinghaus J: Acid-base balance nomogram—A Boston-Copenhagen détente. Anesthesiology 1976;45:539–541PubMedCrossRefGoogle Scholar
  43. 43.
    Siggaard-Andersen O: The pH, log pCO2 blood acid-base nomogram revised. Scand J Clin Lab Invest 1962; 14:598–604CrossRefGoogle Scholar
  44. 44.
    Siggaard-Andersen O: Blood acid-base alignment nomogram. Scand J Clin Lab Invest 1963; 15:211–217CrossRefGoogle Scholar
  45. 45.
    Severinghaus JW: Blood gas calculator. J Appl Physiol 1966;21/1108–1116PubMedGoogle Scholar
  46. 46.
    Visser BF, Maas AHJ: The pH-log PCO2 diagram of separated human blood plasma. Clin Chim Acta 1960;5:850–852PubMedCrossRefGoogle Scholar
  47. 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;6:31–33PubMedCrossRefGoogle Scholar
  48. 48.
    Bunker J: Great trans-Atlantic acid-base debate. Anesthesiology 1965;25:591–594Google Scholar
  49. 49.
    Schwartz WB, Relman AS: A critique of the parameters used in evaluation of acid-base disorders. New Eng J Med 1963:268:1382–1388PubMedCrossRefGoogle Scholar
  50. 50.
    Cohen JJ, Brackett NC Jr, Schwartz WB: The nature of the carbon dioxide titration curve in the normal dog. J Clin Invest 1964;43:777PubMedCrossRefGoogle Scholar
  51. 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;272:6PubMedCrossRefGoogle Scholar
  52. 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;44:291PubMedCrossRefGoogle Scholar
  53. 53.
    Brackett NC Jr. Wingo CF, Muren O, Solano JT: Acidbase response to chronic hypercapnia in man. New Eng J Med 1969;280:124–130PubMedCrossRefGoogle Scholar
  54. 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;268:917–922PubMedCrossRefGoogle Scholar
  55. 55.
    Michel CC, Lloyd BB, Cunningham DJC: The in vivo carbon dioxide dissociation curve of true plasma. Resp Physiol 1966:1:121–137CrossRefGoogle Scholar
  56. 56.
    Prys-Roberts C, Kelman GR, Nunn JF: Determination of the in vivo carbon dioxide titration curve of anaesthetized man. Brit J Anaesth 1966;38:500–509PubMedCrossRefGoogle Scholar
  57. 57.
    Siesjo BK, Messeter K: Factors determining intracellular pH. In: Siesjo BK, Sorensen SK, eds. Ion homeostasis of the brain. Copenhagen: Munksgaard, 1971:245–269Google Scholar
  58. 58.
    Engel K, Kildeberg P, Winters RW: Quantitative displacement of blood acid-base status in acute hypocapnia. Scand J Clin Lab Invest 1969;23:5–17PubMedCrossRefGoogle Scholar
  59. 59.
    Roos A, Thomas LT: The in vitro and in vivo carbon dioxide dissociation curves ot true plasma. Anesthesiology 1967;28:1048–1063PubMedCrossRefGoogle Scholar
  60. 60.
    Engel K, Dell RB, Rahill WJ, et al: Quantitative displacement of acid-base equilibrium in chronic respiratory acidosis. J Appl Physiol 1968;24:288–295PubMedGoogle Scholar
  61. 61.
    Siggaard-Andersen O: An acid-base chart for arterial blood with normal and pathophysiological reference areas. Scand J Clin Lab Invest 1971;27:239–245PubMedCrossRefGoogle Scholar
  62. 62.
    Levesque P, Severinghaus JW: The Boston-Copenhagen détente. Anesthesiology 1977;47:232–234PubMedCrossRefGoogle Scholar
  63. 63.
    Severinghaus JW, Stupfel M, Bradley AF: Variations of pK′ with pH and temperature. J Appl Physiol 1956; 9:197–200PubMedGoogle Scholar
  64. 64.
    Kelman GR, Coleman AJ, Nunn JF: Evaluation of a microtonometer used with a capillary glass pH electrode. J Appl Physiol 1966;21:1103–1107PubMedGoogle Scholar
  65. 65.
    Kelman GR, Nunn JF: Nomograms for correction of blood PO2, PCO2, pH and base excess for time and temperature. J Appl Physiol 1966;21:1484PubMedGoogle Scholar
  66. 66.
    Eisenman G, Bates R, Mattock G, Friedman SM: The glass electrode. New York: Interscience, 1966:1–318Google Scholar
  67. 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; 17:614–616PubMedCrossRefGoogle Scholar
  68. 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;65:445–455Google Scholar
  69. 69.
    Siggaard-Andersen O: Factors affecting the liquid junction potential in electrometric blood pH measurement. Scand J Clin Lab Invest 1961;13:205–211CrossRefGoogle Scholar
  70. 70.
    Siggaard-Andersen O: The first dissociation exponent of carbonic acid as a function of pH. Scand J Clin Lab Invest 1962; 14:587–597CrossRefGoogle Scholar
  71. 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; 67:516–519PubMedGoogle Scholar
  72. 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;21:26–39PubMedGoogle Scholar
  73. 73.
    Semple SJG: Observed pH differences of blood and plasma with different bridge solutions. J Appl Physiol 1961; 16:576–577PubMedGoogle Scholar
  74. 74.
    Peterson JI, Goldstein SR, Fitzgerald RV, Buckhold DK: Fiber optic pH probe for physiologic use. Anal Chem 1980:52:864–869PubMedCrossRefGoogle Scholar
  75. 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;42:323–329PubMedCrossRefGoogle Scholar
  76. 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; 41:333–338PubMedCrossRefGoogle Scholar
  77. 77.
    Eisenman G: Glass electrodes for hydrogen and other cations. New York: Dekker, 1967:1–288Google Scholar
  78. 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. 79.
    Davenport HW: The ABC of acid-base chemistry. 6th ed. Chicago: University of Chicago Press, 1974:1–130Google Scholar
  80. 80.
    Henderson LJ: Blood as a physicochemical system. J Biol Chem 1921, 46:411Google Scholar
  81. 81.
    Filley GF: Acid-base and blood gas regulation. Philadelphia: Lea & Febiger, 1971:1–213Google Scholar
  82. 82.
    Saris NE: International Federation of Clinical Chemistry: Recommendations and Related Documents. New York: Walter de Gruyter, 1984:124–132Google Scholar

Copyright information

© Little, Brown and Company, Inc. 1985

Authors and Affiliations

  • John W. Severinghaus
    • 1
  • Poul B. Astrup
    • 2
  1. 1.Department of AnesthesiaUniversity of California Medical CenterSan Francisco
  2. 2.Department of Clinical ChemistryRigshospital, University of CopenhagenCopenhagenDenmark

Personalised recommendations