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 fa ctors involved in the control of altitude polycythemia were studied. T en 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 Blood was withdrawn in normoxia (N) and after 1 wk (H1), 2 wk (H2), or 3 wk (H3) at 6,542 m for the measurement of serum erythro poietin (EPO), blood hemoglobin (Hb), hematocrit (Hct), intraerythrocy te folate (Fol), and plasma ferritin (Fer) concentrations. Renal blood flow (RBF) and absolute proximal reabsorption rate (APR) were measure d by the p-aminohippuric acid and lithium clearance, respectively, in N and H2 conditions. O-2 supply to the kidneys was calculated using RB F 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. Incr ease 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 hypoxi a. Iron intake in food was markedly decreased during the 2-wk ascent t o 6,542 m. EPO was inversely related to Ca-O2 and positively related t o 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 f rom H2 to H3, despite a high EPO, may be due to a chronically reduced substrate (iron) availability, as suggested by the decrease in Fer fav ored by a low iron intake. We conclude that there is a great interindi vidual variability in erythropoiesis response to EPO in hypoxia. Facto rs 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.