Handling of tracer bicarbonate by the liver. The relative impermeability of hepatocyte cell membranes to the ionic species.

The multiple indicator dilution technique was used to study transfer of labeled HCO3- across the hepatocyte membrane in the anesthetized mongrel dog. A bolus of H[14C]O3-, 51Cr-labeled erythrocytes, [36Cl-] and/or [3H]sucrose, and [3H]OH was injected through a catheter in the portal vein, and timed anaerobic blood samples were obtained from a catheter in the hepatic vein. Experiments were carried out in untreated controls and after intravenous infusion of acetazolamide (100 mg/kg). In the controls, the H[14C]O3- curve was very similar to the [3H]OH curve. The dilution curves were all linear transformations of each other, indicating that HCO3-, as had previously been shown for the other diffusible tracers, undergoes delayed-wave flow-limited distribution. The distribution space for H[14C]O3- in the control situation includes the blood plasma and interstitial spaces, the erythrocyte interior modified by a Donnan equilibrium, and the available liver cellular space. The calculated HCO3- concentration in the liver cells was somewhat lower than that in the plasma space; the difference implied a cellular pH lower than that of plasma by approximately 0.08 pH units. When the carbonic anhydrases were inhibited with acetazolamide, the dilution curve for H[14C]O3- changed radically, approaching that for [36Cl-], which does not enter the liver cells. The change indicates that although HCO3-, like Cl-, is rapidly exchanged between plasma and erythrocytes, it also does not readily penetrate hepatocytes unless previously transformed to carbon dioxide by the carbonic anhydrases.