Skip to main content

Advertisement

SpringerLink
Log in

Red blood cell rheology in sepsis

  • Review
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Changes in red blood cell (RBC) function can contribute to alterations in microcirculatory blood flow and cellular dysoxia in sepsis. Decreases in RBC and neutrophil deformability impair the passage of these cells through the microcirculation. While the role of leukocytes has been the focus of many studies in sepsis, the role of erythrocyte rheological alterations in this syndrome has only recently been investigated. RBC rheology can be influenced by many factors, including alterations in intracellular calcium and adenosine triphosphate (ATP) concentrations, the effects of nitric oxide, a decrease in some RBC membrane components such as sialic acid, and an increase in others such as 2,3 diphosphoglycerate. Other factors include interactions with white blood cells and their products (reactive oxygen species), or the effects of temperature variations. Understanding the mechanisms of altered RBC rheology in sepsis, and the effects on blood flow and oxygen transport, may lead to improved patient management and reductions in morbidity and mortality.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.

Similar content being viewed by others

References

  1. Friedman G, Silva E, Vincent JL (1998) Has the mortality of septic shock changed with time? Crit Care Med 26:2078–2086

    Google Scholar 

  2. Hinshaw LB (1996) Sepsis/septic shock: participation of the microcirculation: an abbreviated review. Crit Care Med 24:1072–1078

    CAS  PubMed  Google Scholar 

  3. Chien S (1982) Rheology in the microcirculation in normal and low flow states. Adv Shock Res 8:71–80

    CAS  PubMed  Google Scholar 

  4. Voerman HJ, Fonk T, Thijs LG (1989) Changes in hemorheology in patients with sepsis or septic shock. Circ Shock 29:219–227

    CAS  PubMed  Google Scholar 

  5. Voerman HJ, Groeneveld AB (1989) Blood viscosity and circulatory shock. Intensive Care Med 15:72–78

    CAS  PubMed  Google Scholar 

  6. Baskurt OK, Gelmont D, Meiselman HJ (1998) Red blood cell deformability in sepsis. Am J Respir Crit Care Med 157:421–427

    CAS  PubMed  Google Scholar 

  7. Yodice PC, Astiz ME, Kurian BM, Lin RY, Rackow EC (1997) Neutrophil rheologic changes in septic shock. Am J Respir Crit Care Med 155:38–42

    CAS  PubMed  Google Scholar 

  8. Ellsworth ML, Forrester T, Ellis CG, Dietrich HH (1995) The erythrocyte as a regulator of vascular tone. Am J Physiol 269:H2155–H2161

    CAS  PubMed  Google Scholar 

  9. Ellsworth ML (2000) The red blood cell as an oxygen sensor: what is the evidence? Acta Physiol Scand 168:551–559

    Google Scholar 

  10. Jagger JE, Bateman RM, Ellsworth ML, Ellis CG (2001) Role of erythrocyte in regulating local O2 delivery mediated by hemoglobin oxygenation. Am J Physiol 280:H2833–H2839

    CAS  Google Scholar 

  11. Somer T, Meiselman HJ (1993) Disorders of blood viscosity. Ann Med 25:31–39

    CAS  PubMed  Google Scholar 

  12. Bishop JJ, Nance PR, Popel AS, Intaglietta M, Johnson PC (2001) Effect of erythrocyte aggregation on velocity profiles in venules. Am J Physiol 280:H222–H236

    CAS  Google Scholar 

  13. Berliner AS, Shapira I, Rogowski O, Sadees N, Rotstein R, Fusman R, Avitzour D, Cohen S, Arber N, Zeltser D (2000) Combined leukocyte and erythrocyte aggregation in the peripheral venous blood during sepsis. An indication of commonly shared adhesive protein(s). Int J Clin Lab Res 30:27–31

    Google Scholar 

  14. Mohandas N (1991) The red blood cell membrane. In: Hoffman R, Benz EJ, Shattil SJ, Furie B, Cohen HJ (eds) Hematology: basis, principles and practice. Churchill-Livingstone, New York, pp 264–269

  15. Lux SE (1979) Dissecting the red cell membrane skeleton. Nature 281:426–429

    CAS  PubMed  Google Scholar 

  16. Mohandas N, Chasis JA (1993) Red blood cell deformability, membrane material properties and shape: regulation by transmembrane, skeletal and cytosolic proteins and lipids. Semin Hematol 30:171–192

    CAS  PubMed  Google Scholar 

  17. Chien S (1977) Principles and techniques for assessing erythrocyte deformability. Blood Cells 3:71–99

    Google Scholar 

  18. Mohandas N, Chasis JA, Shohet SB (1983) The influence of membrane skeleton on red cell deformability, membrane material properties, and shape. Semin Hematol 20:225–242

    CAS  PubMed  Google Scholar 

  19. Piagnerelli M, Zouaoui Boudjeltia K, Brohee D, Piro P, Vincent JL (2000) Comparison of red cell shape in healthy and septic patients by flow cytometry. Intensive Care Med 26[Suppl 3]:S322 [abstr]

  20. Piagnerelli M, Zouaoui Boudjeltia K, Vanhaeverbeek M, Piro P, Vincent JL, Carlier E, Lejeune P (2000) Decrease of red blood cell deformability determined by flow cytometry. Am J Respir Crit Care Med 161:A882 [abstr]

    Google Scholar 

  21. Grebe R, Wolff H, Schmid-Schonbein H (1988) Influence of red cell surface charge on red cell membrane curvature. Pflugers Arch 413:77–82

    CAS  PubMed  Google Scholar 

  22. Piper RD, Pitt-Hyde M, Li F, Sibbald WJ, Potter RF (1996) Microcirculatory changes in rat skeletal muscle in sepsis. Am J Respir Crit Care Med 154:931–937

    CAS  PubMed  Google Scholar 

  23. Lam C, Tyml K, Martin C, Sibbald W (1994) Microvascular perfusion is impaired in a rat model of normotensive sepsis. J Clin Invest 94:2077–2083

    PubMed  Google Scholar 

  24. Tyml K, Yu J, McCormack DG (1998) Capillary and arteriolar responses to local vasodilators are impaired in a rat model of sepsis. J Appl Physiol 84:837–844

    CAS  PubMed  Google Scholar 

  25. Astiz ME, DeGent GE, Lin RY, Rackow EC (1995) Microvascular function and rheologic changes in hyperdynamic sepsis. Crit Care Med 23:265–271

    CAS  PubMed  Google Scholar 

  26. Powell RJ, Machiedo GW, Rush BFJ (1993) Decreased red blood cell deformability and impaired oxygen utilization during human sepsis. Am Surg 59:65–68

    CAS  PubMed  Google Scholar 

  27. Hurd TC, Dasmahapatra KS, Rush BFJ, Machiedo GW (1988) Red blood cell deformability in human and experimental sepsis. Arch Surg 123:217–220

    CAS  PubMed  Google Scholar 

  28. Baskurt OK, Temiz A, Meiselman HJ (1997) Red blood cell aggregation in experimental sepsis. J Lab Clin Med 130:183–190

    CAS  PubMed  Google Scholar 

  29. Pearson MJ, Lipowsky HH (2000) Influence of erythrocyte aggregation on leukocyte margination in postcapillary venules of rat mesentery. Am J Physiol 279:H1460–H1471

    CAS  Google Scholar 

  30. Vincent JL (2000) Update on sepsis: pathophysiology and treatment. Acta Clin Belg 55:79–87

    CAS  PubMed  Google Scholar 

  31. Simchon S, Jan KM, Chien S (1987) Influence of reduced red cell deformability on regional blood flow. Am J Physiol 253:H898–H903

    CAS  PubMed  Google Scholar 

  32. Eichelbronner O, Sielenkamper A, Cepinskas G, Sibbald WJ, Chin-Yee IH (2000) Endotoxin promotes adhesion of human erythrocytes to human vascular endothelial cells under conditions of flow. Crit Care Med 28:1865–1870

    PubMed  Google Scholar 

  33. Langenfeld JE, Livingston DH, Machiedo GW (1991) Red cell deformability is an early indicator of infection. Surgery 110:398–403

    CAS  PubMed  Google Scholar 

  34. Chung TW, O'Rear EA, Whitsett TL, Hinshaw LB, Smith MA (1991) Survival factors in a canine septic shock model. Circ Shock 33:178–182

    CAS  PubMed  Google Scholar 

  35. Han YY, Murtagh BM, Venkataraman ST (1999) 2,3 diphosphoglycerate increases with critical illness in children. Crit Care Med 27[Suppl]:A71 [abstr]

  36. Suzuki Y, Nakajima T, Shiga T, Maeda N (1990) Influence of 2,3-diphosphoglycerate on the deformability of human erythrocytes. Biochim Biophys Acta 1029:85–90

    Article  CAS  PubMed  Google Scholar 

  37. Vincent JL, Zhang H, Szabo C, Preiser JC (2000) Effects of nitric oxide in septic shock. Am J Respir Crit Care Med 161:1781–1785

    CAS  PubMed  Google Scholar 

  38. Graf J, Eichelbrönner O, Sibbald WJ (1999) The red blood cell and nitric oxide. In: Vincent JL (ed) Yearbook of intensive care and emergency medicine. Springer, Heidelberg, pp 465–475

  39. Jia L, Bonaventura C, Bonaventura J, Stamler JS (1996) S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature 380:221–226

    CAS  PubMed  Google Scholar 

  40. Sprague RS, Stephenson AH, Dimmitt RA, Weintraub NL, Branch CA, McMurdo L, Lonigro AJ, Weintraub NA (1995) Effect of L-NAME on pressure-flow relationships in isolated rabbit lungs: role of red blood cells. Am J Physiol 269:H1941–H1948

    CAS  PubMed  Google Scholar 

  41. Sprague RS, Ellsworth ML, Stephenson AH, Lonigro AJ (1996) ATP: the red blood cell link to NO and local control of the pulmonary circulation. Am J Physiol 271:H2717–H2722

    CAS  PubMed  Google Scholar 

  42. Marikovsky Y (1996) The cytoskeleton in ATP-depleted erythrocytes: the effect of shape transformation. Mech Ageing Dev 86:137–144

    Article  CAS  PubMed  Google Scholar 

  43. Busse R, Ogilvie A, Pohl U (1988) Vasomotor activity of diadenosine triphosphate and diadenosine tetraphosphate in isolated arteries. Am J Physiol 254:H828–H832

    CAS  PubMed  Google Scholar 

  44. Miseta A, Bogner P, Berenyi E, Kellermayer M, Galambos C, Wheatley DN, Cameron IL (1993) Relationship between cellular ATP, potassium, sodium and magnesium concentrations in mammalian and avian erythrocytes. Biochim Biophys Acta 1175:133–139

    Article  CAS  PubMed  Google Scholar 

  45. Ismail NH, Cohn EJJ, Mollitt DL (1997) Nitric oxide synthase inhibition negates septic-induced alterations in cytoplasmic calcium homeostasis and membrane dynamics. Am Surg 63:20–23

    CAS  PubMed  Google Scholar 

  46. Deliconstantinos G, Villiotou V, Stavrides JC, Salemes N, Gogas J (1995) Nitric oxide and peroxynitrite production by human erythrocytes: a causative factor of toxic anemia in breast cancer patients. Anticancer Res 15:1435–1446

    CAS  PubMed  Google Scholar 

  47. Ghigo D, Todde R, Ginsburg H, Costamagna C, Gautret P, Bussolino F, Ulliers D, Giribaldi G, Deharo E, Gabrielli G (1995) Erythrocyte stages of Plasmodium falciparum exhibit a high nitric oxide synthase (NOS) activity and release an NOS-inducing soluble factor. J Exp Med 182:677–688

    CAS  PubMed  Google Scholar 

  48. Jubelin BC, Gierman JL (1996) Erythrocytes may synthesize their own nitric oxide. Am J Hypertens 9:1214–1219

    Article  CAS  PubMed  Google Scholar 

  49. Korbut R, Gryglewski RJ (1993) Nitric oxide from polymorphonuclear leukocytes modulates red blood cell deformability in vitro. Eur J Pharmacol 234:17–22

    Article  CAS  PubMed  Google Scholar 

  50. Starzyk D, Korbut R, Gryglewski RJ (1997) The role of nitric oxide in regulation of deformability of red blood cells in acute phase of endotoxaemia in rats. J Physiol Pharmacol 48:731–735

    PubMed  Google Scholar 

  51. Bateman RM, Jagger JE, Sharpe MD, Ellsworth ML, Mehta S, Ellis CG (2001) Erythrocyte deformability is a nitric oxide-mediated factor in decreased capillary density during sepsis. Am J Physiol 280:H2848–H2856

    CAS  Google Scholar 

  52. Mallozzi C, Di Stasi AM, Minetti M (1997) Peroxynitrite modulates tyrosine-dependent signal transduction pathway of human erythrocyte band 3. FASEB J 11:1281–1290

    CAS  PubMed  Google Scholar 

  53. Shiga T, Sekiya M, Maeda N, Kon K, Okazaki M (1985) Cell age-dependent changes in deformability and calcium accumulation of human erythrocytes. Biochim Biophys Acta 814:289–299

    Article  CAS  PubMed  Google Scholar 

  54. Ortiz-Carranza O, Miller ME, Adragna NC, Lauf PK (1997) Alkaline pH and internal calcium increase Na+ and K+ effluxes in LK sheep red blood cells in Cl--free solutions. J Membr Biol 156:287–295

    Article  CAS  PubMed  Google Scholar 

  55. Lau YT, Hsieh CC, Liu MS, Hwang TL, Chen MF, Cheng HS (1994) Erythrocyte Ca2+ pump is defective during sepsis. Circ Shock 44:121–125

    CAS  PubMed  Google Scholar 

  56. Todd JC, Mollitt DL (1995) Effect of sepsis on erythrocyte intracellular calcium homeostasis. Crit Care Med 23:459–465

    PubMed  Google Scholar 

  57. Todd JC, Mollitt DL (1995) Leukocyte modulation inhibits endotoxin-induced disruption of intracellular calcium homeostasis. J Trauma 39:1148–1151

    CAS  PubMed  Google Scholar 

  58. Sowemimo-Coker SO, Debbas NM, Kovacs IB, Turner P (1985) Ex vivo effects of nifedipine, nisoldipine and nitrendipine on filterability of red blood cells from healthy volunteers. Br J Clin Pharmacol 20:152–154

    Google Scholar 

  59. Fujita J, Tsuda K, Takeda T, Yu L, Fujimoto S, Kajikawa M, Nishimura M, Mizuno N, Hamamoto Y, Mukai E, Adachi T, Seino Y (1999) Nisoldipine improves the impaired erythrocyte deformability correlating with elevated intracellular free calcium-ion concentration and poor glycaemic control in NIDDM. Br J Clin Pharmacol 47:499–506

    Google Scholar 

  60. Bergfeld GR, Forrester T (1992) Release of ATP from human erythrocytes in response to a brief period of hypoxia and hypercapnia. Cardiovasc Res 26:40–47

    CAS  PubMed  Google Scholar 

  61. Durocher JR, Payne RC, Conrad ME (1975) Role of sialic acid in erythrocyte survival. Blood 45:11–20

    CAS  PubMed  Google Scholar 

  62. Piagnerelli M, Zouaoui Boudjeltia K, Brohee D, Piro P, Carlier E, Vincent JL, Lejeune P, Vanhaeverbeek M (2003) Alterations of red blood cell shape and sialic acid membrane content in septic shock. Crit Care Med (in press)

  63. Rogers ME, Williams DT, Niththyananthan R, Rampling MW, Heslop KE, Johnston DG (1992) Decrease in erythrocyte glycophorin sialic acid content is associated with increased erythrocyte aggregation in human diabetes. Clin Sci (Colch ) 82:309–313

    Google Scholar 

  64. Mazzanti L, Rabini RA, Salvolini E, Tesei M, Martarelli D, Venerando B, Curatola G (1997) Sialic acid, diabetes, and aging: a study on the erythrocyte membrane. Metabolism 46:59–61

    CAS  PubMed  Google Scholar 

  65. Chari SN, Nath N (1984) Sialic acid content and sialidase activity of polymorphonuclear leucocytes in diabetes mellitus. Am J Med Sci 288:18–20

    CAS  PubMed  Google Scholar 

  66. Chiarini A, Fiorilli A, Di Francesco L, Venerando B, Tettamanti G (1993) Human erythrocyte sialidase is linked to the plasma membrane by a glycosylphosphatidylinositol anchor and partly located on the outer surface. Glycoconj J 10:64–71

    CAS  PubMed  Google Scholar 

  67. Milligan TW, Baker CJ, Straus DC, Mattingly SJ (1978) Association of elevated levels of extracellular neuraminidase with clinical isolates of type III group B streptococci. Infect Immun 21:738–746

    CAS  PubMed  Google Scholar 

  68. Todd JC, Poulos ND, Davidson LW, Mollitt DL (1993) Role of the leukocyte in endotoxin-induced alterations of the red cell membrane. Second place winner of the Conrad Jobst Award in the Gold Medal paper competition. Am Surg 59:9–12

    PubMed  Google Scholar 

  69. Betticher DC, Keller H, Maly FE, Reinhart WH (1993) The effect of endotoxin and tumour necrosis factor on erythrocyte and leucocyte deformability in vitro. Br J Haematol 83:130–137

    CAS  PubMed  Google Scholar 

  70. Machiedo GW, Powell RJ, Rush BFJ, Swislocki NI, Dikdan G (1989) The incidence of decreased red blood cell deformability in sepsis and the association with oxygen free radical damage and multiple-system organ failure. Arch Surg 124:1386–1389

    CAS  PubMed  Google Scholar 

  71. Goode HF, Webster NR (1993) Free radicals and antioxidants in sepsis. Crit Care Med 21:1770–1776

    CAS  PubMed  Google Scholar 

  72. Drost EM, Kassabian G, Meiselman HJ, Gelmont D, Fisher TC (1999) Increased rigidity and priming of polymorphonuclear leukocytes in sepsis. Am J Respir Crit Care Med 159:1696–1702

    CAS  PubMed  Google Scholar 

  73. Kirschenbaum LA, Aziz M, Astiz ME, Saha DC, Rackow EC (2000) Influence of rheologic changes and platelet-neutrophil interactions on cell filtration in sepsis. Am J Respir Crit Care Med 161:1602–1607

    CAS  PubMed  Google Scholar 

  74. Schmid-Schonbein GW, Usami S, Skalak R, Chien S (1980) The interaction of leukocytes and erythrocytes in capillary and postcapillary vessels. Microvasc Res 19:45–70

    CAS  PubMed  Google Scholar 

  75. Bellingan G (2000) Leukocytes: friend or foe. Intensive Care Med 26[Suppl 1]:S111–S118

    Google Scholar 

  76. Claster S, Chiu DT, Quintanilha A, Lubin B (1984) Neutrophils mediate lipid peroxidation in human red cells. Blood 64:1079–1084

    CAS  PubMed  Google Scholar 

  77. Davies KJ, Goldberg AL (1987) Oxygen radicals stimulate intracellular proteolysis and lipid peroxidation by independent mechanisms in erythrocytes. J Biol Chem 262:8220–8226

    CAS  PubMed  Google Scholar 

  78. Hirayama T, Folmerz P, Hansson R, Jonsson O, Pettersson S, Roberts D, Schersten T (1986) Effect of oxygen free radicals on rabbit and human erythrocytes. Studies on cellular deformability. Scand J Thorac Cardiovasc Surg 20:247–252

    CAS  PubMed  Google Scholar 

  79. Uyesaka N, Hasegawa S, Ishioka N, Ishioka R, Shio H, Schechter AN (1992) Effects of superoxide anions on red cell deformability and membrane proteins. Biorheology 29:217–229

    CAS  PubMed  Google Scholar 

  80. Powell RJ, Machiedo GW, Rush BFJ, Dikdan G (1991) Oxygen free radicals: effect on red cell deformability in sepsis. Crit Care Med 19:732–735

    CAS  PubMed  Google Scholar 

  81. Powell RJ, Machiedo GW, Rush BFJ, Dikdan G (1989) Effect of alpha-tocopherol on red cell deformability and survival in sepsis. Curr Surg 46:380–382

    CAS  PubMed  Google Scholar 

  82. Singh M, Stoltz JF (2002) Influence of temperature variation from 5 degrees C to 37 degrees C on aggregation and deformability of erythrocytes. Clin Hemorheol Microcirc 26:1–7

    PubMed  Google Scholar 

  83. Artmann GM, Kelemen C, Porst D, ldt B, Chien S (1998) Temperature transitions of protein properties in human red blood cells. Biophys J 75:3179–3183

    CAS  PubMed  Google Scholar 

  84. Baskurt OK, Mat F (2000) Importance of measurement temperature in detecting the alterations of red blood cell aggregation and deformability studied by ektacytometry: a study on experimental sepsis in rats. Clin Hemorheol Microcirc 23:43–49

    CAS  PubMed  Google Scholar 

  85. Jagger JE, Ellis CG, Sibbald W, Eichelbrönner O (2001) Measurement temperature plays a pivotal role in the distribution of erythrocyte deformability after LPS. Biorheology 38:439–448

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Intensive Care, Erasme University Hospital, Free University of Brussels, 808 route de Lennik, 1070, Brussels, Belgium

    M. Piagnerelli & J.-L. Vincent

  2. Experimental Medicine Laboratory, André Vésale Hospital, Montigny-le-Tilleul, Belgium

    K. Zouaoui Boudjeltia & M. Vanhaeverbeek

Authors
  1. M. Piagnerelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Zouaoui Boudjeltia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Vanhaeverbeek
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J.-L. Vincent
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J.-L. Vincent.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Piagnerelli, M., Boudjeltia, K.Z., Vanhaeverbeek, M. et al. Red blood cell rheology in sepsis. Intensive Care Med 29, 1052–1061 (2003). https://doi.org/10.1007/s00134-003-1783-2

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-003-1783-2

Keywords

Search

Navigation