Regulation of haemoglobin concentration at high altitude

2023/12/05 by Christoph Siebenmann, Johanna Roche, Maja Schlittler +3 · 32 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Anatomy #Biology #Blood volume #Chemistry #Dietary Effects on Health #Effects of high altitude on humans #Endocrinology #Erythropoietin #Hemoglobinopathies and Related Disorders #High Altitude and Hypoxia #Hypoxia (environmental) #Internal medicine #Medicine #Oxygen #Physiology #Plasma volume

paper · pdf · doi:10.1113/jp284578

published in The Journal of Physiology 602(21), 5587-5600 (Wiley)

openalex publication_date 2023/12/05 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06

Abstract

Lowlanders sojourning for more than 1 day at high altitude (HA) experience a reduction in plasma volume (PV) that increases haemoglobin concentration and thus restores arterial oxygen content. If the sojourn extends over weeks, an expansion of total red cell volume (RCV) occurs and contributes to the haemoconcentration. While the reduction in PV was classically attributed to an increased diuretic fluid loss, recent studies support fluid redistribution, rather than loss, as the underlying mechanism. The fluid redistribution is presumably driven by a disappearance of proteins from the circulation and the resulting reduction in oncotic pressure exerted by the plasma, although the fate of the disappearing proteins remains unclear. The RCV expansion is the result of an accelerated erythropoietic activity secondary to enhanced renal erythropoietin release, but a contribution of other mechanisms cannot be excluded. After return from HA, intravascular volumes return to normal values and the normalisation of RCV might involve selective destruction of newly formed erythrocytes, although this explanation has been strongly challenged by recent studies. In contrast to acclimatised lowlanders, native highlanders originating from the Tibetan and the Ethiopian plateaus present with a normal or only mildly elevated haemoglobin concentration. Genetic adaptations blunting the erythropoietic response to HA exposure have been proposed as an explanation for the absence of more pronounced haemoconcentration in these populations, but new evidence also supports a contribution of a larger than expected PV. The functional significance of the relatively low haemoglobin concentration in Tibetan and Ethiopian highlanders is incompletely understood and warrants further investigation.

Citations

• Plasma volume contraction at altitude: where does the plasma go?

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