By Professor P. Astrup

Prof.P.ASTRUP the father of the pH electrode during a conference that was held in ROME in december 1996

There are three fundamentally important compounds for the occurrence of life on our planet: water, oxygen and carbon dioxide, and they are all involved in the metabolism of hydrogen ions. Water is necessary for the appearance of hydrogen ions; oxygen is necessary for the maintenance of the internal fire in the animal kingdom by the continuous burning of nutrients, leading to the formation of hydrogen ions from volatile and non-volatile acids, which are excreted as soon as possible through lungs, gills, kidneys, etc. They are continuously reused in the building up of the vegetable kingdom by the photosynthetic process. Without hydrogen ions life on hearth would not have developed in the way it did. In my speech today I shall concentrate on a few important steps in the development of our knowledge to the hydrogen ions - from the early days of physics, chemistry, physiology, and medicine to our days' complicated instrumentalization of clinical care.

According to a Chinese report, strong acids were known in India in the seventh century A. D. It was described as a wondrous liquid, sometimes cold, sometimes hot, it could dissolve wood, herbs, gold and iron, and if one held it in one's hand, the hand would waste away. From India the skill of making mineral acids was handed down to the Arabs and reached Europe in the thirteenth century.

The strong bases are mentioned in Hindu literature from the eight century. They were made from the ash of burned wood, by the Arabs called "al quali", or by burning lime.

Acids and bases were very important for the development of chemistry from the praxis of gold-making into a scientific discipline. There were various ways of explaining their actions, but an all-important change in the conceptions was introduced with the theory of electrolytic dissociation enunciated in 1887 by Svante Arrhenius in Sweden. Nobody in Sweden, however, believed in his ideas, but Jacobus van't Hoff in Amsterdam and Wilhelm Ostwald in Riga did, and now the Swedes acknowledged the ideas and awarded Arrhenius the Nobel Prize in 1903.

Strong acids had, since Volta in 1800 discovered how to make an electrical current, been used for this purpose in European physical laboratories, leading to the construction of the so-called "gas cells". They consisted of platinized platinium electrodes in glass tubes in contact with oxygen and hydrogen respectively, and immersed in dilute sulphuric acid. Wilhem Ostwald discovered that the decisive factor for the generation of the current was the concentration of hydrogen ions and hydroxide ions formed by the two gasses. This led him to employ hydrogen electrodes to determine the dissociation constant of water, a factor of primary concern in physical chemistry.

Ostwald was very proud of this achievement and reported it at a meeting of the Royal Saxonian Scientific Society on 9 January 1893.

His work was of the greatest importance for the development of not only physics and chemistry, but particularly of the biological and medical sciences, with Lawrence Henderson, professor of physiology at Harvard, and S.P. L. Sørensen, professor at the Carlsberg Laboratories in Copenhagen, as the pioneers. The life work of Henderson concentrated on giving a description of the many variables influencing the neutrality of blood, since its most significant and most conspicuous property was its ability to neutralise large amounts of acids or bases without losing its neutral reaction. Sørensen in Copenhagen worked with the enzymatic break down of proteins and demonstrated the vital importance of pH control to the enzymatic process. He introduced the concept of "buffer" and further the term "hydrogen ion exponent" which he symbolised by "pH". Both concepts were immediately accepted by the scientific world.

One of Sørensen's pupils was the young Danish physiologist K. A. Hasselbalch, who in 1917 by using a hydrogen electrode was the first to measure correct pH values of blood at 37 degrees centigrade. He became interested in medical acid/bases disorders and was the first to distinguish between metabolic and respiratory disturbances, which could be compensated or uncompensated according to the measured blood pH value. His name is used in the well-known Henderson-Hasselbalch equation, expressing the buffering action of bicarbonate/carbonic acid in blood.

However, measuring of blood pH values at 37 degrees centigrade with a hydrogen electrode was far too difficult for hospitals in the first half of this century - and still is! Before 1920 only a few of the more advanced university hospitals had small research laboratories belonging to the medical departments, and laboratory analyses to support the routine clinical examinations were few. However, the introduction of insulin for treating diabetes created a need for blood sugar analyses and for diagnosing diabetic acidosis. Now small clinical laboratories began to appear. Donald D. van Slyke's methods for determining the total amount of carbon dioxide in serum were chosen as the most reliable ones for diagnosing acidosis, and in the 1930'ies and 1940'ies his gasometric measuring instruments were found in most of the clinical laboratories. The name alkali reserve or bicarbonate were used to characterise a measured result: low values signified a metabolic acidosis, high values a metabolic alkalisis. The metabolic disturbances were considered as the most important to diagnose, since a correct treatment could be lifesaving. The respiratory acid/base disorders were relatively rare, caused usually only minor changes in the alkali reserve values, and treatment dealt with changes of the alveolar ventilation. Therefore it was often soon forgotten in clinical departments that the total content of CO2 in serum, as measured by the van Slyke equipment, was not synonymous with the alkali reserve, but was dependent also on the actual carbon dioxide tension.

At least it was so at the fever hospital in Copenhagen, where a severe polio epidemic began in August 1952. The incidence of respiratory paralysis was unusually high, and after the first couple of weeks 27 of 31 patients treated in respirators had died. The situation was desperate, and the epidemic was still in its beginning. At that time I was, as head of the laboratory of the hospital, summoned from my summer holidays in order to attend a conference with the anæsthesiologist Bjørn Ibsen and the hospital's clinicians to discuss the causes of the deaths. The patients were well oxygenated by the time of death, and the only objective indication was a high level of "bicarbonate" in blood as measured in a van Slyke apparatus. The clinicians believed that the patients had a metabolic alkalosis of mysterious origin. Ibsen promptly dismissed this suggestion and argued that it could just as well be caused by carbon dioxide retention. Quickly executed determinations of blood pH at 37 degrees centigrade soon proved him right, and on the following day a patient was tracheotomized and given manual positive pressure ventilation which immediately caused the "alkalosis" to disappear. Subsequently, this treatment was used on all patients having respiratory paralyses.

This outright misinterpretation of a high CO2 content of serum as alkalosis in patients with respiratory insufficiency made a deep impression on me as a laboratory doctor, and lead to new ideas of how to measure on blood for obtaining acid/base parameters which were correct in chemical and physical aspects and easy to understand and use by the clinicians in their daily work.

After some years of work at my department in Copenhagen we ended up first with a macro method using 2-3 mL of blood and later with a micromethod requiring as little as 50-75 microlitres of blood, which in a couple of minutes could give all the relevant values for expressing an acid/base status of the blood.

We had constructed the whole equipment, except the pH-meter, in my department at the University Hospital in Copenhagen, and now offered it to Radiometer. However, the directors here had become tired of physicians' and hospitals' continuous claim for service, so they were not interested in manufacturing it. However, a brother of one of the directors was a strong believer in the revolutionary power of ideas, so at Radiometer it constructed a piece of equipment in secret. It was looking and functioning so well that the directors finally decided to manufacture it. The success was obvious.

Before I finish I should like to add that another polio epidemic, in USA in 1954, led Richard Stow at the Ohio State University in Columbus to the construction of a pCO2 electrode. Leland Clark in USA, working in a team using cardiopulmonary bypass, discovered in 1953 that membrane covered oxygen electrodes did not suffer from oxygen poisoning, and this led to the construction of the oxygen electrodes which we use in our hospitals today.