Control of erythropoiesis after high altitude acclimatization

Abstract

Erythropoiesis was studied in 11 subjects submitted to a 4-h hypoxia (HH) in a hypobaric chamber (4,500 m, barometric pressure 58.9 kPa) both before and after a 3-week sojourn in the Andes. On return to sea level, increased red blood cells (+3.27%), packed cell volume (+4.76%), haemoglobin (+6.55%) ( P<0.05), and increased arterial partial pressure of oxygen (+8.56%), arterial oxygen saturation (+7.40%) and arterial oxygen blood content ( C(a)O(2)) (+12.93%) at the end of HH ( P<0.05) attested high altitude acclimatization. Reticulocytes increased during HH after the sojourn only (+36.8% vs +17.9%, P<0.01) indicating a probable higher reticulocyte release and/or production despite decreased serum erythropoietin (EPO) concentrations (-46%, P<0.01). Hormones (thyroid, catecholamines and cortisol), iron status (serum iron, ferritin, transferrin and haptoglobin) and renal function (creatinine, renal, osmolar and free-water clearances) did not significantly vary (except for lower thyroid stimulating hormone at sea level, P<0.01). Levels of 2,3-diphosphoglycerate (2,3-DPG) increased throughout HH on return (+14.7%, P<0.05) and an inverse linear relationship was found between 2,3-DPG and EPO at the end of HH after the sojourn only ( r=-0.66, P<0.03). Inverse linear relationships were also found between C(a)O(2) and EPO at the end of HH before ( r=-0.63, P<0.05) and after the sojourn ( r=-0.60, P=0.05) with identical slopes but different ordinates at the origin, suggesting that the sensitivity but not the gain of the EPO response to hypoxia was modified by altitude acclimatization. Higher 2,3-DPG levels could partly explain this decreased sensitivity of the EPO response to hypoxia. In conclusion, we show that altitude acclimatization modifies the control of erythropoiesis not only at sea level, but also during a subsequent hypoxia.

Physical Activity at Altitude: Challenges for People With Diabetes

“…This increase is associated with prolonged stay at very high and extreme altitudes. Polycythemia, in the context of increased erythrocyte mass due to stimulated erythropoietin production, is an important risk factor for stroke (36,37). Theoretically, the increased risk of dehydration and vascular disorders in patients with diabetes superimposed on the effects of altitude (hypoxia, increased viscosity, and hypocapnia causing cerebral vasoconstriction) may render patients with type 2 diabetes particularly at risk for stroke at very high and extreme altitudes.…”

Stability of oxyhemoglobin affinity in patients with obstructive sleep apnea-hypopnea syndrome without daytime hypoxemia

“…The shortest period of hypoxia sufficient to induce a significant rise in blood 2,3-DPG is unknown, but it appears from this study that short hypoxemic episodes in OSAHS are not sufficient to result in any significant rise in 2,3-DPG and thereby in a shift of the ODC. Data from experimental hypobaric hypoxia exposures showed a small but significant increase in DPG after 2.5 h of sustained hypoxia (15). However, one must keep in mind that other factors may produce a shift of the ODC and changes in 2,3-DPG levels; during apnea and hypopnea, the resulting alveolar hypoventilation increases arterial PCO 2 and lowers the pH.…”

“…This phenomenon has been well documented in various conditions of persistent hypoxia from nonpulmonary origin, and this adaptation was regarded as a mechanism of protection against tissue hypoxia. The increase in 2,3-DPG was documented in healthy subjects submitted to hypobaric hypoxia (8,15) and in patients with chronic anemia (17), cyanotic congenital heart disease (12), and heart failure (2). However, the role of 2,3-DPG in patients with hypoxemia from pulmonary origin is still debated, mainly because of opposite effects of hypoxemia and respiratory alkalosis on 2,3-DPG (7).…”

Reticulocytes in untreated Obstructive Sleep Apnoea

“…Most of our knowledge about the relationship between hypoxaemia and EPO has been obtained through studies on prolonged hypoxaemia. Experimental studies on intermittent hypoxaemia in humans, mainly performed in athletes, evaluated the effects of hypoxic exposure for a few hours a day, and showed conflicting results not only as regards EPO but also reticulocytes release: a few investigations showed both an increase in reticulocytes and in EPO [32][33][34], other studies found an increase in reticulocytes without a concomitant increase in EPO [35][36], and another group reported an increase in EPO without a concomitant increase in reticulocytes [37][38][39]. However, intermittent hypoxaemia of OSA consists of sequences of short hypoxic episodes, usually lasting less than a minute, separated by even shorter normoxic intervals, recurring up to hundreds of times each night during sleep.…”