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

1. There is an increase of intestinal iron absorption during the early period of exposure to an altitude of 14,900 feet. After 48 hours of exposure, this was estimated to be about 3 times higher than the absorption observed in subjects at 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 2 hours of arrival to 14,900 feet, indicating that the increase in the production of red cells, to compensate for hypoxia, is a very early response.

3. The highest increase in plasma and red cell iron turnover rate takes place 7 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 of high altitudes (14,900 feet) have a red cell iron turnover rate of approximately 30 per cent higher than healthy subjects at sea level.

4. A progressive decrease in the plasma and red cell iron turnover rate is observed 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 great degree of depression on red cell production. After that, a gradual return to normal rate is observed in the weeks that follow.

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

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

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

8. The life span of the red blood cells, after descent from high altitudes to sea level, falls within normal patterns. However, by the method employed it is not possible to determine if there is an increased destruction of red cells during the first week. But if there is a greater destruction, this would be of a small degree, affecting only the older elements. The increase in the hemoglobin breakdown pigments, which occurs under the influence of environmental factors, 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 in newcomers to high altitudes rise and reach a peak at the end of the second month, followed by a gradual decline. On the other hand, when high altitude natives are brought down to sea level, a marked decrease in erythroprotoporphyrins is noted. The rate of decrease is highest within the first months.

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