NOTA SULLA NON LINEARITÀ DEL SISTEMA RESPIRATORIO: COME L’EMOGLOBINA LEGA GASTON TISSANDIER A REINHOLD MESSNER

This article starts from an aeronautical tragedy to track briefly the history of the oxygen equilibrium curve and the creation of Hill’s model of it. After having argued that the characteristics of such a curve determine the non-linear behaviour of the respiratory system, I discussed some functional consequences of this behaviour, which explain how it happened that Reinhold Messner succeeded in the extraordinary enterprise of climbing Mount Everest without supplementary oxygen.

The Bohr/Haldane effect: a model-based uncovering of the full extent of its impact on O2 delivery to and CO2 removal from tissues

For a century, the influence of the Bohr effect on the utilization of blood-borne oxygen has been deemed secondary to its influence on the uptake of carbon dioxide by the blood. Here, we show that the opposite is the case. Using a simple two-ligand, two-state formulation, we modeled the simultaneous oxygen and proton binding to hemoglobin, as well as the resulting acid-base changes of the surrounding solution. Blocking of the Bohr effect in this model system results in a dramatic increase in the oxygen affinity, as expressed by the oxygen partial pressure at half saturation, the P50. It also becomes clear that the P50 and the Bohr factor (a measure of the size of the Bohr effect) are not independent but directly related. Thus, everything else being equal, varying the number of Bohr groups from 0 to 8 per tetramer results in an increase in the Bohr factor from 0 to −0.9 and an increase in P50 from 6 to 46 mmHg at a constant Pco2 of 40 mmHg. Therefore, changes in hemoglobin structure that lead to changes in the Bohr factor will inevitably also change hemoglobin oxygen affinity. NEW & NOTEWORTHY Using a mathematical model, we show that the Bohr effect has a more profound effect on gas exchange than is evident when comparing oxygen equilibrium curves measured in the laboratory at different constant values of Pco2 or pH. Protons preloaded on the Bohr groups, as well as the protons taken up during oxygen unloading, dramatically decrease oxygen affinity of the physiological oxygen equilibrium curve. Therefore, the Bohr effect is instrumental in setting the oxygen affinity.

Effect of haemoglobin concentration on the oxygen affinity of intact lamprey erythrocytes

We investigated whether the oxygen affinity of lamprey haemoglobin decreases with increasing oxygen concentration at the high (10­25 mmol l-1 monomeric) haemoglobin concentrations prevailing within the erythrocytes. The intracellular concentration of haemoglobin was experimentally adjusted by shrinking the cells osmotically: the osmolality of the equilibration medium was increased from approximately 250 mosmol kg-1 by 90 mosmol kg-1 to 340 mosmol kg-1 or by 180 mosmol kg-1 to 430 mosmol kg-1 by adding sucrose in the medium. This increased the mean cellular haemoglobin concentration from 16.9±0.23 mmol l-1 (monomeric haemoglobin) to 20.0±0.20 mmol l-1 (monomeric haemoglobin) and to 23.0±0.36 mmol l-1 (monomeric haemoglobin), respectively (means ± s.e.m., N=35­40; all the samples from 7­8 different pools of blood at each osmolality combined). The oxygen equilibrium curves at each osmolality were determined by Tucker's method. An increase in haemoglobin concentration shifted the oxygen equilibrium curve to the right as indicated by the P50 values, which were 4.26±0.07 kPa at the lowest, 4.64±0.13 kPa at the intermediate and 5.64±0.40 kPa (means ± s.e.m., N=7­8) at the highest haemoglobin concentrations. The decrease in haemoglobin oxygen-affinity was attributed to the volume changes, since the intracellular pH did not decrease with increasing mean cellular haemoglobin concentration. Thus, the variations in red blood cell volume commonly observed during hypoxia may play a role in the regulation of haemoglobin function.