Hypoxia-induced hemoglobinemia: hypoxic threshold and pathogenic mechanism

The effects of chronic exposure to graded hypoxia (inspired PO2 = 146, 90, 78, 73 and 60 torr) on the development of hypoxia-induced hemoglobinemia and the rate of hemoglobin degradation in intact and acutely splenectomized rats were studied. Hemoglobin mass increased with hypoxia over the whole range studied. Hemoglobinemia was not detectable until the inspired PO2 reached 78 torr, and became much more severe at inspired PO2 = 73 and 60 torr. The increased rate of hemoglobin degradation measured as bilirubin excretion, was largely accounted for by circulating red cell destruction at inspired PO2 = 146, 90 and 78 torr. However, the rate of hemoglobin degradation exceeded the estimated circulating red cell destruction by more than 100% at inspired PO2 = 73 and 60 torr. Acute splenectomy reduced both hemoglobinemia and the "extra" bilirubin production by 80%. The data suggest that 1) the hypoxic threshold for the occurrence of hypoxia-induced hemoglobinemia lies at inspired PO2 = 90 to 80 torr; 2) ineffective erythropoiesis is the most likely pathogenic mechanism of the hemoglobinemia and the "extra" bilirubin production and 3) the spleen plays a primary role in these phenomena.