Medicine of the Future in America

The Oxyhemoglobin Dissociation Curve in Liver Cirrhosis: Recommendation

We attribute the increased dispersion of the Po2 values in our cirrhotic patients to four factors: (1) Alterations in the activities of enzymes controlling the phosphoglycerate shunt are observed in liver cirrhosis: glucokinase activity is low or absent, hexokinase increases, and the glucokinase/hexokinase ratio is reduced. Glucose-6-phosphatase is also lower in cirrhotics. In alcoholic liver cirrhosis and primary biliary cirrhosis, the activity of glucokinase is < 10 of the activity in control subjects. (2) Thyroxine stimulates 2,3 DPG synthesis; hypothyroidism is present in 7% to 20% of patients with primary biliary cirrhosis. 2,3 DPG was not measured in these patients, but it is likely that its concentration was decreased and therefore that the ODC was shifted to the left. (3) Plasma ions are disturbed in cirrhosis: for instance, sodium and water excretion are im-paired, especially in the presence of ascites and when diuretics are administered. Hyponatremia or hypernatremia and hypokalemia are frequently present. In our results, disturbed plasma ions in cirrhotic patients included sodium, calcium, and potassium (Table 4).

It is likely that these alterations contributed to increase the dispersion of the Po2 values for different levels of So2%. However, they did not contribute to determine the P50 (Table 3, last equation). (4) Various drugs are administered to cirrhotic patients: diuretics influence the position of the ODC, and propranolol alters hemoglobin affinity in patients with coronary artery disease by a mechanism not mediated by 2,3 DPG. Above 80% saturation, the ODC dispersions of the two groups are identical, and therefore the loading of oxygen from pulmonary alveoli to hemoglobin was normal in cirrhotic patients. However, as all our cirrhotic patients were anemic, a leftward shift of the ODC had a detrimental effect on tissue oxygenation. We do not know the pattern of the ODC during exercise, which is accompanied by a marked increase in oxygen consumption. Finally, some tissues are highly sensitive to hypoxia.
The two conditions for revealing an abnormal increase of the Po2 dispersion are an appropriate methodology and a homogeneous group of patients. This implies that factors other than pH, temperature, carbon dioxide content, and organic phosphates are able to influence the position of the ODC. This must stimulate a search for more factors than the four factors mentioned above, for instance plasma ions, diuretics, and propranolol.
Leaving aside carbon monoxide intoxication and hemoglobinopathies (such as  thalassemia, human hemoglobin with abnormal affinity, and impaired heme-heme interaction such as hemoglobin Warsaw or South Milwaukee),> three patterns for the ODC have been described: (1) a leftward shift induced by hypothermia, alkalosis, or RBC hexoki-nase deficiency; (2) a rightward shift mediated by hyperthermia, acidosis, or an increased synthesis of 2,3 DPG induced by chronic hypoxia or thyroxine intake; and (3) normal ODC and 2,3 DPG despite severe hypoxemia of chronic lung disease. Based on our observations, we propose a fourth pattern: a normal mean ODC with an increased dispersion of Po2 values at different levels of So2%.

This entry was posted in Liver disease and tagged liver cirrhosis, oxyhemoglobin dissociation curve.
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