Medicine of the Future in America

The Oxyhemoglobin Dissociation Curve in Liver Cirrhosis: Research

The Oxyhemoglobin Dissociation Curve in Liver Cirrhosis: ResearchWe have already described the same pattern, ie, a normal mean ODC and an increased dispersion of the Po2 values for different levels of So2% in patients with chronic obstructive lung disease27 and in patients with severe comorbid illnesses. When the patients of this last group were treated, their ODC normalized, suggesting that the increased dispersion is reversiЫe. Why does the dispersion of Po2 values for different levels of So2% increase in patients with cirrhosis? Synthesis and breakdown of 2,3 DPG are controlled by several enzymes in the phosphoglycerate cycle of Rapoport and Luebering, a side-shuttle of the main Embden-Meyerhoff pathway36 (Fig 3).

Factors controlling synthesis and breakdown of 2,3 DPG include the following: (1) The concentration of 2.3    DPG itself: a negative feedback mechanism inhibits the activity of the phosphoglycerate mu-tase.37 (2) Hydrogen ion concentration: in alkalosis, the rate of glycolysis is increased and the activity of 2.3    DPG phosphatase decreases; therefore, 2,3 DPG is increased.38 As a matter of fact, the 2,3 DPG level is negatively correlated with hydrogen ion concentration, pH being significantly higher in cirrhotics than in control subjects. This fact had likely induced a 2,3 DPG synthesis, thus a rightward shift of the ODC (Fig 4). (3) Inorganic phosphate concentration: 2,3 DPG is low in hypophosphatemia and high in hyperphosphatemia. In cirrhotic patients, it is likely that the increase in inorganic phosphate induced a rightward shift of the ODC by two concomitant mechanisms: a direct action of plasma ions on hemoglobm, and a stimulation of 2,3 DPG synthesis.

The production of 2,3 DPG is also stimulated by anemia, high-altitude hypoxia, heart failure, chronic obstructive lung diseases, sleep apnea syndrome, and ARDS. The 2,3 DPG level of our cirrhotic patients was not correlated with the Pa02 or So2% but rather with the saturation in the mixed venous blood. This correlation has been described by Woodson et al, who investigated 39 patients with noncyanotic heart disease and found that the 2,3 DPG rise was due to an increased amount of deoxygenated hemoglobin in venous blood.


Figure 3. The Embden-Meyerhoff pathway with the Rapaport-Luebering shunt. ATP = adenosine triphosphate; ADP = adenosine diphosphate.


Figure 4. Relationship between 2,3 DPG and P50 in cirrhotic patients.

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