Modifications of the Acid-Base Status of the Internal Milieu of Tumors

Abstract

In 5 different types of rat tumors, the pH of the interstitial fluid ranged from 7.193 to 6.948, the CO₂ tension from 59 to 84 mm Hg, the dissolved CO₂ from 2.0 to 2.6 mM per liter, and the concentration of bicarbonate from 18.6 to 24.3 mM per liter. Compared with the plasma of blood afferent to the tumor, the pH of the tumor interstitial fluid was 0.2 to 0.4 units lower, the pCO₂ 16 to 39 mm Hg higher, the dissolved CO₂ about 1 mM per liter higher, and the concentration of bicarbonate 4 to 6 mM per liter lower. The same differences were observed when the tumor interstitial fluid was compared with the interstitial fluid of the normal subcutaneous area, though the differences were slightly less when the comparison was made with the plasma of the efferent blood of the tumor or with the lymph of the thoracic duct of the host. A change in the acid-base status of the interstitial fluid of the tumor was produced either by an increase of the CO₂ concentration in the air inhaled by the host or by ingestion of sodium bicarbonate or ammonium chloride. When a depression of pH was produced in the blood plasma, a depression roughly equal was found in the interstitial fluid of the tumor. As the pH of this fluid is normally quite low, exceptionally low pH values (6.6–6.7) could be induced exclusively in the tumor. The CO₂ tension increased in the tumor to levels twice as high as that in plasma or in the other body fluids of the host, and values of more than 200 mm Hg were reached in the interstitial fluid of the tumor. The amount of dissolved CO₂ changed proportionally while the concentration of the bicarbonate showed less drastic oscillations. A peculiarity of NaHCO₃ was that it acted as an acidifying agent exclusively in the interstitial fluid of the tumor. Profound changes were produced in the milieu of the tumor, though in the other fluids of the host the parameters of the acid-base equilibrium remained at a level that was physiologically safe.