CONTROL OF ERYTHROPOIESIS IN HUMANS DURING PROLONGED EXPOSURE TO THE ALTITUDE OF 6,542-M

Altitude hypoxia induces an increase in erythropoeisis. Some of the factors involved in the control of altitude polycythemia were studied. Ten subjects (4 women, 6 men) were exposed for 3 wk to extreme altitude (6,542 m). Blood was withdrawn in normoxia (N) and after 1 wk (H1), 2 wk (H2), or 3 wk (H3) at 6,542 m for the measurement of serum erythropoietin (EPO), blood hemoglobin (Hb), hematocrit (Hct), intraerythrocyte folate (Fol), and plasma ferritin (Fer) concentrations. Renal blood flow (RBF) and absolute proximal reabsorption rate (APR) were measured by the p-aminohippuric acid and lithium clearance, respectively, in N and H2 conditions. O-2 supply to the kidneys was calculated using RBF and arterial O-2 content (Ca-O2). After an initial sharp increase in EPO, it decreased at H2 and H3. Hct and Hb increased from N to H1 and H2 and then unexpectedly decreased from H2 to H3. Mean corpuscular Hb content (MCHC = Hb/Hct) was lower in all H than in N conditions. Increase in EPO at H1 varied from 3- to 134-fold among individuals. Women showed a smaller increase in Hct and Hb and a greater decrease in MCHC. Two women showed a large increase in EPO without increase in Hb. Fol was not modified by altitude hypoxia. Fer showed a marked decrease in H1 and H3 compared with N. Hb was positively related to Fer in hypoxia. Iron intake in food was markedly decreased during the 2-wk ascent to 6,542 m. EPO was inversely related to Ca-O2 and positively related to APR. The increase in Hb at H1 may have restored the O-2 availability in the kidneys and reduced the formation of EPO. The decrease in Hb from H2 to H3, despite a high EPO, may be due to a chronically reduced substrate (iron) availability, as suggested by the decrease in Fer favored by a low iron intake. We conclude that there is a great interindividual variability in erythropoiesis response to EPO in hypoxia. Factors involved in the modulation of this response include nutritional and sex differences, iron stores, and tubular function that determines O-2 supply to renal sensors responsible for EPO secretion.