Regulation of Red Blood Cell Volume with Exercise Training

Abstract

Hypervolemia is a hallmark of endurance training (ET) and manifests by similar elevations in plasma (PV) and red blood cell volume (RBCV) so that hematocrit largely remains unaltered following weeks/months of training. While the mechanisms facilitating PV expansion with ET have been previously reviewed extensively this is not the case for RBCV. Endurance champions may have 40% more RBCV than controls and RBCV may increase up to 10% following months of regular exercise training in healthy individuals. Such adaptations are the main factor leading to concomitant changes in maximal oxygen uptake. The increase in RBCV is preceded by that of PV after few ET sessions, which in turn transiently decreases the hematocrit. The “critmeter” theory suggests that O 2 sensors located within the juxtamedullary apparatus regulate the hematocrit via modulation of renal erythropoietin (EPO) production according to arterial O 2 content‐dependent changes in tissue O 2 pressure. Hence, the initial decrease in hematocrit can be considered as a primary mechanism facilitating RBCV expansion with ET. Furthermore, after a single endurance exercise bout blood volume‐regulating hormones ANGII and VPN increase transiently. Both stimulate renal EPO production. Catecholamines and cortisol, stress hormones acutely increased by endurance exercise, may facilitate the release of red blood cells from the bone marrow, thus possibly contributing to ET‐induced erythropoiesis. These and other endocrine effects could be enhanced by the hyperplasia of the hematopoietic bone marrow observed in endurance athletes. © 2019 American Physiological Society. Compr Physiol 9:149‐164, 2019.

Relationship between plasma volume and essential blood constituents in patients with heart failure and preserved ejection fraction

“…Of note, the formation or red blood cells, that is erythropoiesis, are governed by the hormone Epo, which is primarily regulated by arterial O 2 content and synthesized in peritubular fibroblast-like cells in the kidney (Jelkmann, 1992;Wu et al, 1995;Lundby et al, 2014). Conforming with the fact that arterial O 2 content is known to be inversely related to hemodilution (low Hb concentration) and therefore to PV (Montero & Lundby, 2018;Montero & Lundby, 2019), we found a positive relationship between PV and circulating Epo in HFpEF patients. Conforming with the fact that arterial O 2 content is known to be inversely related to hemodilution (low Hb concentration) and therefore to PV (Montero & Lundby, 2018;Montero & Lundby, 2019), we found a positive relationship between PV and circulating Epo in HFpEF patients.…”

<p>Evaluation of Hypoglycemic Therapy Through Physical Exercise in n5STZ-Induced Diabetes Rats</p>

“…In some situations, a hematocrit increase may cause a chronic myeloproliferative disturbance due to the abnormal clonal multiplication of pluripotent hematopoietic progenitor cells in the absence of recognizable physiological stimuli, in which super production of erythrocytes occur. 43 However, no signs of this disturbance were identified in the animals, even with significance in hematocrit values. A possible explanation for erythroid hemoconcentration in diabetic animals would be associated with water and electrolyte mobilization in the muscle tissue due to the exercise.…”

Did you know—why does maximal oxygen uptake increase in humans following endurance exercise training?

“…Less salient, albeit fundamental adaptations, ~10% increments in BV, are observed after several weeks to months of ET in previously untrained individuals . Once BV becomes stabilized for a given dose of ET, the two major blood volumetric components, ie, plasma volume (PV) and RBCV, are proportionally augmented thus leaving haematocrit (Htc) roughly unaltered . The crucial role of BV expansion in VO 2max responses to ET is evidenced when post‐training PV and RBCV are restored to pre‐training levels via phlebotomy, a procedure that abolishes increases in maximal cardiac output (Q max ) and VO 2max , notwithstanding the presence of enhanced skeletal muscle capillarization and mitochondrial biogenesis .…”

“…RBCV expansion augments the capacity to deliver O 2 , and thereby VO 2max , via two mechanisms: (i) larger total BV facilitates venous return and cardiac filling, which by means of the Frank‐Starling mechanism leads to increased stroke volume and Q max , and (ii) higher number of circulating red blood cells and specifically, the haemoglobin inside them, preserves blood O 2 carrying capacity, which would be otherwise reduced because of PV expansion . While the fact that VO 2max is mainly determined by RBCV and haemoglobin mass (Hb mass ) is generally accepted, little attention has been devoted to the mechanisms that regulate erythropoiesis with ET . Specifically, the question arises as to whether erythropoiesis is optimally stimulated by ET.…”

“…It should be noted that Epo is mostly produced by kidney peritubular fibroblast‐like cells and regulated by O 2 ‐dependent pathways, whose activities are ultimately contingent upon arterial O 2 content . The increase of circulating Epo with ET may essentially be triggered by post‐exercise PV expansion and the resultant decrease in arterial O 2 content in a negative feedback loop attempting to maintain normal Htc and O 2 carrying capacity . Haematological adaptations to ET may thus aim for homeostasis rather than to increase O 2 transport capacity and VO 2max .…”