RED BLOOD CELL ADAPTATIONS INDUCED BY EXERCISE

  • Radoš Stefanović Institute For Medical Research, National Institute of Republic of Serbia
  • Biljana Ristić University of Belgrade, Institute for Medical Research, National Institute of Republic of Serbia, Group for Immunology, Belgrade, Serbia
  • Ivana Drvenica Grupa za imunologiju, Institut za medicinska istraživanja, Univerzitet u Beogradu
Keywords: erythrocytes, training, deformability, erythropoiesis, hemorheology

Abstract


Exercise significantly increases blood flow and perfusion in active muscles to enhance oxygen and nutrient delivery. These enhanced demands affect blood rheology and red blood cell (RBC) characteristics, leading to specific adaptations. These adaptations are influenced by exercise type, intensity, frequency, duration, and individual characteristics of subject population (gender, age, nutritional status etc.).

This review aims to comprehensively summarize the different adaptations of erythrocytes to short-term and long-term exercise, as well as the mechanisms of their occurrence, considering the influence of various factors.

The results from the previous research indicate that regular exercise enhances the metabolic, structural, and functional capabilities of RBCs. These adaptations include improved energy balance, increased cell turnover rate, improved membrane stability, as well as better antioxidative defense. Despite potential risks such as "sports anemia", exercise also affects the dynamics of hemoglobin and iron concentrations, as well as the appearance of extracellular hemoglobin. Overall, the literature highlights the critical role of exercise in maintaining optimal erythrocyte function, improving circulation, and overall health, offering potential therapeutic benefits.

Through a critical review of literature data on the influence of exercise on the characteristics and functions of erythrocytes, this paper can be a useful guideline for the interpretation of clinically significant results in physically active individuals.

Author Biography

Ivana Drvenica, Grupa za imunologiju, Institut za medicinska istraživanja, Univerzitet u Beogradu

Senior research associate in the Group for Immunology.

She graduated from the Faculty of Pharmacy at the University of Belgrade - Pharmaceutical Technology module.

PhD in Biotechnology and Biochemical Engineering, Faculty of Technology and Metallurgy, University of Belgrade.

References

Cho YI, Mooney MP, Cho DJ. Hemorheological disorders in diabetes mellitus. J Diabetes Sci Technol. 2008;2(6):1130-8. doi: 10.1177/1932296808002006.

Lippi G, Sanchis-Gomar F. Epidemiological, biological and clinical update on exercise-induced hemolysis. Ann Transl Med. 2019;7(12). doi: 10.21037/atm.2019.05.41.

Paraiso LF, Gonçalves-e-Oliveira AFM, Cunha LM, de Almeida Neto OP, Pacheco AG, Araújo KBG, et al. Effects of acute and chronic exercise on the osmotic stability of erythrocyte membrane of competitive swimmers. PLoS One. 2017;12(2):e0171318. doi: 10.1371/journal.pone.0171318.

Pospieszna B, Kusy K, Slominska EM, Zieliński J. Life-long sports engagement enhances adult erythrocyte adenylate energetics. Sci Rep. 2021;11(1):23759. doi: 10.1038/s41598-021-03275-y.

Van Wijk R, Van Solinge WW. The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis. Blood. 2005;106(13):4034-42. doi: 10.1182/blood-2005-04-1622.

De la Fuente IM, Cortés JM, Valero E, Desroches M, Rodrigues S, Malaina I, et al. On the dynamics of the adenylate energy system: homeorhesis vs homeostasis. PLoS One. 2014;9(10):e108676. doi: 10.1371/journal.pone.0108676.

Dudzinska W, Suska M, Lubkowska A, Jakubowska K, Olszewska M, Safranow K, et al. Comparison of human erythrocyte purine nucleotide metabolism and blood purine and pyrimidine degradation product concentrations before and after acute exercise in trained and sedentary subjects. J Physiol Sci. 2018;68:293-305. doi: 10.1007/s12576-017-0536-x.

Pospieszna B, Kusy K, Słomińska EM, Dudzinska W, Ciekot-Sołtysiak M, Zieliński J. The effect of training on erythrocyte energy status and plasma purine metabolites in athletes. Metabolites. 2019;10(1):5. doi: 10.3390/metabo10010005.

Racine ML, Dinenno FA. Reduced deformability contributes to impaired deoxygenation‐induced ATP release from red blood cells of older adult humans. J Physiol. 2019;597(17):4503-19. doi: 10.1113/JP278338.

Dudzinska W. Purine nucleotides and their metabolites in patients with type 1 and 2 diabetes mellitus. J Biomed Sci Eng. 2014;7(1):38-44. doi: 10.4236/jbise.2014.71006.

O’Brien III WG, Berka V, Tsai A-L, Zhao Z, Lee CC. CD73 and AMPD3 deficiency enhance metabolic performance via erythrocyte ATP that decreases hemoglobin oxygen affinity. Sci Rep. 2015;5(1):13147. doi: 10.1038/srep13147.

Smith JA. Exercise, training and red blood cell turnover. Sports Med. 1995;19(1):9-31. doi: 10.2165/00007256-199519010-00002.

Lew VL, Tiffert T. On the mechanism of human red blood cell longevity: roles of calcium, the sodium pump, PIEZO1, and gardos channels. Front Physiol. 2017;8:977. doi: 10.3389/fphys.2017.00977.

Ingley E. Erythrocytes. Encyclopedia of Respiratory Medicine, Second Edition: Erythrocytes: Elsevier; 2022. p. 232-7.

Bizjak DA, Tomschi F, Bales G, Nader E, Romana M, Connes P, et al. Does endurance training improve red blood cell aging and hemorheology in moderate-trained healthy individuals? J Sport Health Sci. 2020;9(6):595-603. doi: doi.org/10.1016/j.jshs.2019.02.002.

Sentürk UK, Gündüz F, Kuru O, Koçer G, Ozkaya YG, Yesilkaya A, et al. Exercise-induced oxidative stress leads hemolysis in sedentary but not trained humans. J Appl Physiol (1985). 2005;99(4):1434-41. doi: doi. org/ 10. 1152/ jappl physi ol. 01392. 2004.

Weight LM, Byrne MJ, Jacobs P. Haemolytic effects of exercise. Clin Sci (Lond). 1991;81(2):147-52. doi: 10.1042/cs0810147.

Smith JA, Martin DT, Telford RD, Ballas SK. Greater erythrocyte deformability in world-class endurance athletes. Am J Physiol. 1999;276(6):H2188-93. doi: 10.1152/ajpheart.1999.276.6.H2188.

Schobersberger W, Tschann M, Hasibeder W, Steidl M, Herold M, Nachbauer W, et al. Consequences of 6 weeks of strength training on red cell O 2 transport and iron status. Eur J Appl Physiol Occup Physiol. 1990;60:163-8. doi: 10.1007/BF00839152.

Robinson Y, Cristancho E, Böning D. Intravascular hemolysis and mean red blood cell age in athletes. Med Sci Sports Exerc. 2006;38(3):480-3. doi: 10.1249/01.mss.0000188448.40218.4c.

Falsetti HL, Burke ER, Feld RD, Frederick EC, Ratering C. Hematological variations after endurance running with hard-and soft-soled running shoes. Phys Sportsmed. 1983;11(8):118-27. doi: 10.1080/00913847.1983.11708609.

Telford RD, Sly GJ, Hahn AG, Cunningham RB, Bryant C, Smith JA. Footstrike is the major cause of hemolysis during running. J Appl Physiol (1985). 2003;94(1):38-42. doi: 10.1152/japplphysiol.00631.2001.

Selby GB, Eichner ER. Endurance swimming, intravascular hemolysis, anemia, and iron depletion: new perspective on athlete's anemia. Am J Med. 1986;81(5):791-4. doi: 10.1016/0002-9343(86)90347-5.

Beneke R, Bihn D, Hütler M, Leithäuser RM. Haemolysis caused by alterations of α-and β-spectrin after 10 to 35 min of severe exercise. Eur J Appl Physiol. 2005;95:307-12. doi: 10.1007/s00421-005-0010-y.

Drvenica IT, Stančić AZ, Maslovarić IS, Trivanović DI, Ilić VL. Extracellular hemoglobin: modulation of cellular functions and pathophysiological effects. Biomolecules. 2022;12(11):1708. doi: 10.3390/biom12111708.

Stančić A, Drvenica I, Bugarski B, Ilić V, Bugarski D. Extracellular xenogeneic hemoglobin suppresses the capacity for C2C12 myoblast myogenic differentiation. Arch Biol Sci. 2020;72(3):379-91. doi: doi.org/10.2298/ABS200625032S.

Richieri GV, Mel HC. Temperature effects on osmotic fragility, and the erythrocyte membrane. Biochim Biophys Acta. 1985;813(1):41-50. doi: 10.1016/0005-2736(85)90343-8.

Hiro T. Studies on the osmotic fragility of erythrocytes influenced by a metabolic acidosis. Jap J Phys Fitness Sports Med. 1982;31(5):279-90. doi: 10.7600/jspfsm1949.31.279.

Platt OS, Lux SE, Nathan DG. Exercise-induced hemolysis in xerocytosis. Erythrocyte dehydration and shear sensitivity. J Clin Invest. 1981;68(3):631-8. doi: 10.1172/JCI110297.

Rasmussen H, Lake W, Allen JE. The effect of catecholamines and prostaglandins upon human and rat erythrocytes. Biochim Biophys Acta. 1975;411(1):63-73. doi: 10.1016/0304-4165(75)90285-8.

Yusof A, Leithauser RM, Roth HJ, Finkernagel H, Wilson MT, Beneke R. Exercise-induced hemolysis is caused by protein modification and most evident during the early phase of an ultraendurance race. J Appl Physiol (1985). 2007;102(2):582-6. doi: 10.1152/japplphysiol.00580.2006.

Vitali EDP, Guglielmini C, Casoni I, Vedovato M, Gilli P, Farinelli A, et al. Serum erythropoietin in cross-country skiers. Int J Sports Med. 1988;9(2):99-101. doi: 10.1055/s-2007-1024986.

Montero D, Breenfeldt-Andersen A, Oberholzer L, Haider T, Goetze JP, Meinild-Lundby A-K, et al. Erythropoiesis with endurance training: dynamics and mechanisms. Am J Physiol Regul Integr Comp Physiol. 2017;312(6):R894-R902. doi: 10.1152/ajpregu.00012.2017.

Caldemeyer KS, Smith RR, Harris A, Williams T, Huang Y, Eckert GJ, et al. Hematopoietic bone marrow hyperplasia: correlation of spinal MR findings, hematologic parameters, and bone mineral density in endurance athletes. Radiology. 1996;198(2):503-8. doi: 10.1148/radiology.198.2.8596857.

Shellock FG, Morris E, Deutsch AL, Mink JH, Kerr R, Boden SD. Hematopoietic bone marrow hyperplasia: high prevalence on MR images of the knee in asymptomatic marathon runners. AJR Am J Roentgenol. 1992;158(2):335-8. doi: 10.2214/ajr.158.2.1729795.

Altehoefer C, Schmid A, Büchert M, Ghanem NA, Heinrich L, Langer M. Characterization of hematopoietic bone marrow in male professional cyclists by magnetic resonance imaging of the lumbar spine. J Magn Reson Imaging.2002;16(3):284-8. doi: 10.1002/jmri.10157.

Trivanović DI, Drvenica IT. Bone marrow adipose tissue: impacts on bone marrow stem cell niche and hematopoietic system. Reference Module in Biomedical Sciences: Elsevier; 2024. doi: 10.1016/B978-0-443-15717-2.00096-2.

Dar A, Schajnovitz A, Lapid K, Kalinkovich A, Itkin T, Ludin A, et al. Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells. Leukemia. 2011;25(8):1286-96. doi: 10.1038/leu.2011.62.

Shahani S, Braga-Basaria M, Maggio M, Basaria S. Androgens and erythropoiesis: past and present. J Endocrinol Invest. 2009;32(8):704-16. doi: 10.1007/BF03345745.

Christ ER, Cummings MH, Westwood NB, Sawyer BM, Pearson TC, Sönksen PH, et al. The importance of growth hormone in the regulation of erythropoiesis, red cell mass, and plasma volume in adults with growth hormone deficiency. J Clin Endocrinol Metab. 1997;82(9):2985-90. doi: 10.1210/jcem.82.9.4199.

Ambroży T, Rydzik Ł, Obmiński Z, Błach W, Serafin N, Błach B, et al. The effect of high-intensity interval training periods on morning serum testosterone and cortisol levels and physical fitness in men aged 35–40 years. J Clin Med. 2021;10(10):2143. doi: 10.3390/jcm10102143.

Petraglia F, Barletta C, Facchinetti F, Spinazzola F, Monzani A, Scavo D, et al. Response of circulating adrenocorticotropin, beta-endorphin, beta-lipotropin and cortisol to athletic competition. Acta Endocrinol (Copenh). 1988;118(3):332-6. doi: 10.1530/acta.0.1180332.

Schwarz AJ, Brasel JA, Hintz RL, Mohan S, Cooper DM. Acute effect of brief low-and high-intensity exercise on circulating insulin-like growth factor (IGF) I, II, and IGF-binding protein-3 and its proteolysis in young healthy men. J Clin Endocrinol Metab. 1996;81(10):3492-7. doi: 10.1210/jcem.81.10.8855791.

Bernardino Neto M, de Avelar EB Jr, Arantes TS, Jordão IA, da Costa Huss JC, de Souza TM, et al. Bivariate and multivariate analyses of the correlations between stability of the erythrocyte membrane, serum lipids and hematological variables. Biorheology. 2013;50(5-6):305-20. doi: 10.3233/BIR-130641.

Lemos GSD, Márquez-Bernardes LF, Arvelos LR, Paraíso LF, Penha-Silva N. Influence of glucose concentration on the membrane stability of human erythrocytes. Cell Biochem Biophys. 2011;61(3):531-7. doi: 10.1007/s12013-011-9235-z.

de Freitas MV, Marquez-Bernardes LF, de Arvelos LR, Paraíso LF, Gonçalves E Oliveira AFM, Mascarenhas Netto Rde C, et al. Influence of age on the correlations of hematological and biochemical variables with the stability of erythrocyte membrane in relation to sodium dodecyl sulfate. Hematology. 2014;19(7):424-30. doi: 10.1179/1607845413Y.0000000145.

Drvenica I, Mojsilović S, Stančić A, Marković D, Kovačić M, Maslovarić I, et al. The effects of incubation media on the assessment of the shape of human erythrocytes by flow cytometry: a contribution to mathematical data interpretation to enable wider application of the method. Eur Biophys J. 2021;50(6):829-46. doi: 10.1007/s00249-021-01527-3.

Paraiso LF, de Freitas MV, Gonçalves-E-Oliveira AFM, de Almeida Neto OP, Pereira EA, Mascarenhas Netto RC, et al. Influence of acute exercise on the osmotic stability of the human erythrocyte membrane. Int J Sports Med. 2014:35(13):1072-7. doi: 10.1055/s-0034-1371834.

Kamada T, Tokuda S, Aozaki S, Otsuji S. Higher levels of erythrocyte membrane fluidity in sprinters and long-distance runners. J Appl Physiol (1985). 1993;74(1):354-8. doi: 10.1152/jappl.1993.74.1.354.

Yamada T, Tohori M, Ashida T, Kajiwara N, Yoshimura H. Comparison of effects of vegetable protein diet and animal protein diet on the initiation of anemia during vigorous physical training (sports anemia) in dogs and rats. J Nutr Sci Vitaminol (Tokyo). 1987;33(2):129-49. doi: 10.3177/jnsv.33.129.

Nemkov T, Skinner SC, Nader E, Stefanoni D, Robert M, Cendali F, et al. Acute cycling exercise induces changes in red blood cell deformability and membrane lipid remodeling. Int J Mol Sci. 2021;22(2):896. doi: 10.3390/ijms22020896.

Nader E, Guillot N, Lavorel L, Hancco I, Fort R, Stauffer E, et al. Eryptosis and hemorheological responses to maximal exercise in athletes: Comparison between running and cycling. Scand J Med Sci Sports. 2018;28(5):1532-40. doi: 10.1111/sms.13059.

Kobayashi S, Hamazaki T, Sawazaki S, Nakamura H. Reduction in the ADP release from shear-stressed red blood cells by fish oil administration. Thromb Res.1992;65(3):353-64. doi: 10.1016/0049-3848(92)90166-8.

Spodaryk K. Iron metabolism in boys involved in intensive physical training. Physiol Behav. 2002;75(1-2):201-6. doi: 10.1016/S0031-9384(01)00640-0.

Mariño MM, Grijota FJ, Bartolomé I, Siquier-Coll J, Román VT, Muñoz D. Influence of physical training on erythrocyte concentrations of iron, phosphorus and magnesium. J Int Soc Sports Nutr. 2020;17(1):1-7. doi: 10.1186/s12970-020-0339-y.

Nishiie-Yano R, Hirayama S, Tamura M, Kanemochi T, Ueno T, Hirayama A, et al. Hemolysis is responsible for elevation of serum iron concentration after regular exercises in judo athletes. Biol Trace Elem Res. 2020;197(1):63-9. doi: 10.1007/s12011-019-01981-3.

Novosadova J. The changes in hematocrit, hemoglobin, plasma volume and proteins during and after different types of exercise. Eur J Appl Physiol Occup Physiol. 1977;36(3):223-30. doi: 10.1007/BF00421753.

Published
2024/07/09
Section
Reviews