Altitude

Some patients demonstrate significant symptoms attributable to acutely increased altitude, which can progress to cerebral edema, acute pulmonary edema, and death if not treated. IMG

Altitude adjustment is typically resolved within 21 days. Physiologic changes include increased red blood cell production, seen as a homeostatic adjustment to lower oxygen concentrations at higher elevations.

Observed differences between high altitude-adapted and low altitude adapted populations demonstrate polycythemia and increased uric acid production PMID 12046023. IMG

Purine signalling mediates the differentiation of precursor blood cells, and therefore dictates the final proportions of one blood cell type compared to another. IMG

In a non-targeted comparison of urinary metabolites, an acute deficit of hypoxanthine in those who had altitude sickness was observed PMID 34588992. IMG 

Voxelotor is a new treatment for sickle-cell that increases hemoglobin production, and has a hypoxanthine-similar structure.

Acute altitude sickness is treated by transportation to lower altitude, but also, with acetazolamide, which is xanthine-similar. In combination with hypoxanthine deficit observed in patients with altitude sickness as compared to altitude-changed, but not ill patients, treatment with a xanthine analogue suggests that altitude may increase speed of transit from hypoxanthine (i) to xanthine (x) and uric acid, and that slowing this progression ameliorates altitude sickness. IMG

Suicide risk is correlated with altitude accross the US PMID 21214344. Concern for acute exacerbation of depressive episode with change in altitude is a recognized risk PMID 31343257. Altitude-induced hypoxanthine deficit may deplete inosine causing increased depressive symptoms.  IMG

Parkinson's patients are cautioned against traveling to altitude, due to increased risk of depression PMID 33986595, but also risk of PD progression PMID 34955663, consistent with hypothesis of PD as a disease of purine depletion.  IMG