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Out of Thin Air: The Evolving Enigma of Erythropoietin and Neocytolysis
- Bernard A. Harris, Jr., MD; and
- Paul E. Epstein, MD
- Dr. Harris: The Harris Foundation, Inc.; Houston, TX 77289-0907 Dr. Epstein: University of Pennsylvania; Radnor, PA 19087
In this issue, Rice and colleagues (1) explore the mechanisms underlying a rapid decrease in red cell mass that occurs during descent from high altitude to sea level, a process known as neocytolysis. The sequence of events that they describe is instructive not only for its physiologic implications but also for its demonstration of how keen observation in one setting can be translated into useful knowledge in another. While it seems logical at first to think of altitude on mountains as analogous to altitude in a spacecraft, in reality the environments could not be more dissimilar. Mountainous altitude is characterized by greatly diminished oxygen availability but gravity conditions that are essentially the same as those at sea level, whereas space travel is characterized by the same oxygen availability as at sea level but in a setting of greatly diminished gravity. How, then, can one condition shed light on the other?
The key issues in this paradox appear to be not only what the red cells see but also where the body sees the red cells. On the one hand, mountain dwellers develop increased red cell mass because oxygen delivery is decreased to oxygen sensors in the renal peritubular cells, stimulating the production of an “enhancer-binding factor” for the erythropoietin (EPO) gene. Activation of the EPO gene increases the level of erythropoietin itself, which in turn increases erythrocyte production. On descent to sea level, the increased erythrocyte mass, with its increased oxygen content, signals the kidney to shut down erythropoietin production.
Astronauts, in contrast, encounter the mirror image of this sequence. On entering µgravity, capacitance vessels collapse because the weight of the blood no longer forces the vascular walls apart. Blood is then redistributed centrally, where vascular filling is less dependent on gravity. The heart and kidneys then sense increased …
