Dear Jack:

FIRST:

This is how we are seeing some general medical aspects at our institution:

a) When normal animals or human beings ascend to altitude the two pumps, hemo-dynamic and neumo-dynamic play a fundamental role in acute adaptation to hypoxia as has been nicely described by many authors.

b) In normal and subjects with disease of diverse etiology, the increase of hemoglobin is the most effective mechanism of adaptation.

c) When there is tissue hypoxia, independent of its cause the increase of hemoglobin is closely related with the degree of hypoxia, resembling the altitude effect.

d) This increase in hemoglobin is due, for example, to the presence of pulmonary shunt of varied etiology, from which the principal is anatomo-pathologic lesions as: the destruction, obstruction, or impermeability of the pulmonary alveoli with preservation of the alveoli capillary net. The lesions that more often produce shunt are: the macro and micro thromboembolism due to endothelial damage in the venous system as in phlebitis, certain forms of skin cancer, parasites, smoking, etc.

e) In the lungs the arterialized pulmonary veins blood (already hypoxic due to altitude) mixes with non-arterialized blood of the alveolar shunt, then goes to all organs with  low oxygen tension, unsaturated. The kidney responds with the erythropoyetin and the bone marrow with the erythrocyte production.

f) Adaptation  mechanisms to acute and chronic hypoxia are the same, the only difference is their time of action.

g) The benefit of low ascent is based on the necessary time for hemoglobin to be produced, in order to reach the normal value for a certain altitude.

h) Hemoglobin during hypoxia increases oxygen content (CaO2) and respiration is regulated according to the metabolism at rest and during exercise.  The CaO2 is reduced to the minimum during sleep. Hypoventilation due to “ relative hyperoxia “ at the nervous centers level regulates respiratory frequency.

• OF COURSE, WE DON’T EXCLUDE THE ROLE THAT OTHER SYSTEMS PLAY DURING ADAPTATION,  AS THE NEUROENDOCRINE, THE ADRENAL SYMPATHETIC, AND OTHERS. BUT THIS IS ANOTHER FIELD OF STUDY BEING DONE BY OTHERS.

SECOND:

Thank you so much for your comments on the subject of CaO2 and PaO2 in respiratory control. It is a privilege to exchange ideas in this matter with you.

I will freely express the following points, which are based on observations at our laboratory, which up to now are unfortunately unpublished. Of course, this is only some preliminary opinion.

We have been studying oxygen consumption of yeast and the oxyhemoglobin saturation curve in blood from normals and increased polycythemia, under the same experimental conditions. The difference is that yeast cells take longer to consume the oxygen from the polycythemic blood due to a higher oxygen content in hemoglobin, making the desaturation curve bulky and CaO2 can be calculated by integrating it. Yeast does not stop oxygen consumption down to a very low PO2 and CaO2 in the saturation curve: So you can assume that the same happens with all cells in the tissues.

The affinity of the cells for O2 is of such a degree that a small difference in pressure will be sufficient, depending on their metabolic rate and respiratory coefficient.

We were also studying the differences between normal and increased polycythemia during exercise. During all stages, SaO2 of increased polycythemia remained lower than in normals up to the end of the exercise protocol. The lower saturation reflects the low oxygen tension.  The non-sedentary patients tolerate very well the protocol with very low O2 tensions due to a sufficient amount of oxygen in the CaO2.

THIRD:

 As a consequence, – since nothing is absolute – , the following questions arise:

1) Is the increase of Hb necessary or unnecessary for adaptation to high altitude and particularly in tissue hypoxia due to disease? Can other mechanisms replace the role of Hb?

2) Is there a necessity of a great difference of PaO2  between the red cell  and the tissue cell? 

3) In polycytemia Vera and anemia are the mechanisms of metabolism different? How are the two pumps regulated?

That is what I can say for the moment, there’s more to come.

Gustavo Sr.

July-15-2004