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     

The Hemolytic Anemia of Human Bartonellosis

A study of the processes of formation and destruction of blood has beencarried out, in addition to other investigations of the physiopathology of theanemia of human bartonellosis. From the results obtained the following conclusions may be drawn:

1. The life-span of the red cells parasitized by Bartonella bacilliformis isgreatly shortened. However, not all the parasitized red cells are prematurelydestroyed.

2. Red cells from normal subjects are partially destroyed when they are injected into infected patients. More than 50 per cent of them survive normally.

3. The mechanical fragility of the red cells is increased in the majority ofthe cases.

4. The index of sequestration of red cells by the liver and spleen was increased in the three patients studied. Also, the products of catabolism of hemoglobin were increased in all the patients studied.

5. The increased production of red cells as a response to the great destructionwas prevented at first, but later it reached its peak, being in some cases fivetimes greater than normal.

6. The search for agglutinins and hemolysins was negative.

7. The amount of free protoporphyrins in the red cells was increased, indicating that there was some interference to the synthesis of hemoglobin thatwould also explain the hypochromia of the red cells.

8. The increase in the diameter of the red cells was independent of the actualamount of reticulocytes.

Submitted on November 23, 1960 Accepted on February 12, 1961     

Nutritional Deficiency and Anemia in Latin America: A Collaborative Study

A collaborative study of nutritionalanemia in third trimester pregnancy wasperformed in seven Latin Americancountries. Laboratory measurements included hemoglobin level, mean corpuscular hemoglobin concentration (MCHC),serum iron and iron-binding capacity,serum folate, vitamin B₁₂ and albumin.Iron deficiency (transferrin saturation below 15%) was found in 48% of pregnantwomen, as compared with 21% of nonpregnant females and 3% of male controls of comparable age. The prevalenceof folate deficiency (serum folate below3 ng/ml.) was 10%, 10% and 9% in thesethree groups, respectively. Vitamin B₁₂deficiency (serum level below 80 pg/ml.)was found in 15% of pregnant women,but in less than 1% of both controlgroups. Anemia, as defined by currentWHO criteria, was found in 38.5% ofpregnant women, 17.3% of nonpregnantwomen and 3.9% of men. Analysis of thefrequency distribution for hemoglobinlevels, based on a Gaussian distributionin normal subjects, suggested that a largeportion of subjects considered anemic byWHO criteria were normal and that thetrue incidence of anemia in pregnant andnonpregnant females was 22 and 12%respectively. Correlation analysis indicated that iron deficiency was of majorimportance as a cause of anemia, whilefolate lack was contributory only in pregnancy; no relationship could be demonstrated between vitamin B₁₂ deficiencyand anemia.

Submitted on December 9, 1970 Revised on June 7, 1971 Accepted on June 15, 1971