The polycythemia of high altitudes: iron metabolism and related aspects

Observations on the iron metabolism as related to the influence of a lowoxygen tension at high altitudes, and after the disappearance of this factorupon return to sea level, have been made in human subjects. They consistedmainly of studies of intestinal absorption and turnover rate of iron by meansof the radioactive isotope of this metal (Fe-⁵⁹). Additional observations weremade on blood volume, reticulocytosis, bone marrow cytology, life span ofthe red cells and hemoglobin breakdown pigments. The data obtained seemto justify the following conclusions:

1. There is an increase of intestinal iron absorption during the early periodof exposure to an altitude of 14,900 feet. After 48 hours of exposure, this wasestimated to be about 3 times higher than the absorption observed in subjectsat sea level and in native residents at the above-mentioned altitude.

2. There is an increase of plasma and red cell iron turnover rates after 2hours of arrival to 14,900 feet, indicating that the increase in the productionof red cells, to compensate for hypoxia, is a very early response.

3. The highest increase in plasma and red cell iron turnover rate takes place7 to 14 days after exposure to high altitude begins. After six months of exposure, there is still an elevated iron turnover rate. The native residents ofhigh altitudes (14,900 feet) have a red cell iron turnover rate of approximately30 per cent higher than healthy subjects at sea level.

4. A progressive decrease in the plasma and red cell iron turnover rate isobserved in native residents of high altitudes when brought down to sea level,the maximum of which is reached after two to five weeks, indicating a greatdegree of depression on red cell production. After that, a gradual return tonormal rate is observed in the weeks that follow.

5. The degree of reticulocytosis is in close relationship with changes in thered cell iron turnover rates.

6. Changes in the total blood volume, either during ascent or descent, takeplace only after several weeks. The red cell mass variations which occurduring the early periods of environmental change, are compensated by proportional changes in the plasma volume. The increase or decrease of the totalblood volume after this period is due exclusively to red cell mass modifications.

7. The bone marrow cytologic studies carried out in subjects temporarilyexposed or living permanently at high altitudes show a hyperplastic condition.The reverse, or an inhibition of red cell production, takes place when highaltitude polycythemic subjects are brought down to sea level. This constitutesthe cytologic counter-proof for the iron turnover studies.

8. The life span of the red blood cells, after descent from high altitudes tosea level, falls within normal patterns. However, by the method employed itis not possible to determine if there is an increased destruction of red cellsduring the first week. But if there is a greater destruction, this would be of asmall degree, affecting only the older elements. The increase in the hemoglobin breakdown pigments, which occurs under the influence of environmentalfactors, is also discussed.

9. In native residents of high altitudes the amount of free erythroprotoporphyrins is higher than in residents at sea level. The erythroprotoporphyrins innewcomers to high altitudes rise and reach a peak at the end of the secondmonth, followed by a gradual decline. On the other hand, when high altitudenatives are brought down to sea level, a marked decrease in erythroprotoporphyrins is noted. The rate of decrease is highest within the first months.

Submitted on June 11, 1958 Accepted on September 26, 1958