Shear stress and force required for tether formation of neonatal and adult erythrocytes

Ruef, Peter; Gehm, J; Gehm, Lothar; Pöschl, Johannes

doi:10.3233/ch-2011-1390

Cited by 6 publications

(1 citation statement)

References 24 publications

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“…Narrow capillaries determine the erythrocytes’ flow-induced morphological alterations including the change of the biconcave discoid shape to parachute and slipper shapes observed in microchannels, which serve as idealized microvessels [ 437 , 438 , 439 , 440 , 441 ]. Improvements in experimental technologies using microfluidic models allows for the exact determination of applied shear stress and associated forces toward RBCs, their microcirculatory dynamics, mechanical stability and deformability, heterogeneity in rheological properties, the deformation of molecular architecture as well as hydrodynamic and macromolecule-induced interaction [ 436 , 442 , 443 , 444 , 445 , 446 , 447 , 448 ]. The specific mechanical and hemodynamic properties of RBCs contribute to aiding blood flow especially when exposed to shear forces in the microcirculation that may lead to morphological changes and associated vesicle formation [ 435 ].…”

Section: Erythrocyte Morphology In the Microcirculation And Hemolymentioning

confidence: 99%

Valid Presumption of Shiga Toxin-Mediated Damage of Developing Erythrocytes in EHEC-Associated Hemolytic Uremic Syndrome

Detzner

Pohlentz

Müthing

2020

Toxins

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The global emergence of clinical diseases caused by enterohemorrhagic Escherichia coli (EHEC) is an issue of great concern. EHEC release Shiga toxins (Stxs) as their key virulence factors, and investigations on the cell-damaging mechanisms toward target cells are inevitable for the development of novel mitigation strategies. Stx-mediated hemolytic uremic syndrome (HUS), characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal injury, is the most severe outcome of an EHEC infection. Hemolytic anemia during HUS is defined as the loss of erythrocytes by mechanical disruption when passing through narrowed microvessels. The formation of thrombi in the microvasculature is considered an indirect effect of Stx-mediated injury mainly of the renal microvascular endothelial cells, resulting in obstructions of vessels. In this review, we summarize and discuss recent data providing evidence that HUS-associated hemolytic anemia may arise not only from intravascular rupture of erythrocytes, but also from the extravascular impairment of erythropoiesis, the development of red blood cells in the bone marrow, via direct Stx-mediated damage of maturing erythrocytes, leading to “non-hemolytic” anemia.

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Section: Erythrocyte Morphology In the Microcirculation And Hemolymentioning

confidence: 99%

Valid Presumption of Shiga Toxin-Mediated Damage of Developing Erythrocytes in EHEC-Associated Hemolytic Uremic Syndrome

Detzner

Pohlentz

Müthing

2020

Toxins

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Flow behavior of fetal, neonatal and adult RBCs in narrow (3–6 μm) capillaries – Calculation and experimental application

Ruef

Stadler

Poeschl

2014

Clinical Hemorheology and Microcirculation

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BACKGROUND AND OBJECTIVES: In capillaries with diameters less than those of resting RBCs, the cells have to deform to pass through such narrow vessels. Since RBCs of fetuses, neonates and adults differ in their geometrical properties the flow behavior of RBCs with different sizes in uniform tubes with diameters of 3 to 6 m were studied by means of a micropipette system and a mathematical model. Assumptions in this model include an RBC flow velocity of 1 mm/s, axisymmetric cell shape and a gap between the RBC and the vessel wall that allows sufficient lubrication. The flow resistance depends on the surface area and volume of RBCs, the plasma viscosity and the vessel diameter. METHODS: Surface area and volume of different RBC populations (20 fetuses, 20 preterm neonates, 10 term neonates and 10 adults) were determined by means of a micropipette system and plasma viscosity was measured using a capillary tube viscometer. The flow behavior of RBCs with different volumes (61, 83 and 127 fl) was studied by direct microscopic observation using a micropipette system. The micropipettes had diameters of 3.5, 4.1, 5.1, and 6.0 m. The flow velocity of the RBC in the pipettes was 1 mm/s and the calculated and measured cell lengths were compared. RESULTS: Volume and surface area of RBCs were 140 ± 29 fl and 172 ± 20 m 2 , respectively, in the fetuses, decreased with increasing maturity (term neonates: 110 ± 20 fl and 149 ± 18 m 2 ) and reached the lowest values in adults (93 ± 14 fl and 136 ± 12 m 2 ). Plasma viscosities increased with increasing maturity due to rising plasma protein concentrations. The flow model leads to the following conclusions: During the passage of 3-to 6-m vessels, the large fetal and neonatal RBCs are more elongated than the smaller adult RBCs. The critical vessel diameter, i.e., when the rear of the RBC becomes convex during passage of a narrow capillary, was 4.1 m for fetal RBCs, 3.6 m for neonatal RBCs and 3.3 m adult cells. Suspended in the same medium, fetal and neonatal RBCs require 27% (term neonates) to 100% (fetuses) higher driving pressures than adult RBCs to achieve the necessary elongation for passing through a 4.5-m capillary. However, the different RBCs require similar driving pressures if the cells are suspended in the corresponding autologous plasma. Cell lengths of the RBCs with different geometry determined during the flow experiments agreed with the predicted values. CONCLUSION: We conclude that the large size of fetal and neonatal RBCs may cause impaired flow in narrow vessels with diameters below the critical values of 3.6 to 4.1 m. In vessels with diameters above the critical diameter (D cr ), the disadvantage of the large size of neonatal and fetal RBCs appears to be completely compensated for by the lower plasma viscosity.

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Red blood cell mechanical stability test

Başkurt

Meiselman

2013

Clinical Hemorheology and Microcirculation

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Red blood cells (RBC) are exposed to various levels of shear stress (SS) during their flow in the circulatory system, yet no significant damage occurs if their mechanical stability is not impaired. Alternatively, normal RBC may be damaged during flow in non-physiological environments and under extreme SS (e.g., extracorporeal circulation, ventricular assist devices). The shear-induced damage may result in hemolysis or in altered mechanical properties of RBC that, in turn, reduces the ability of RBC to withstand further damage by SS. An ektacytometer employing a Couette shearing system was used to apply SS at a constant level of 100 Pa for 300 seconds as a model of sub-hemolytic mechanical stress. The degree of cellular damage during and after the application was assessed by diffraction pattern analysis. The area of the diffraction pattern was found to correlate with the number of RBC in the sheared suspension. Monitoring the ellipse area during the application of gradually increasing SS provides the concentration of the remaining intact RBC and can therefore be used to estimate the hemolytic threshold as a measure of RBC mechanical stability. The hemolytic threshold determined after the mechanical stress application was found to be ∼150 Pa, while it was ∼250 Pa in the same samples before the SS application. Additionally, SS-elongation index curves recorded before and after the application of the sub-hemolytic SS significantly differed from each other, indicating the impairment in deformability following the mechanical stress. The Couette type ektacytometer can be used as a tool to assess the sub-hemolytic damage to RBC in testing the biomedical equipment.

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Shear stress and force required for tether formation of neonatal and adult erythrocytes

Cited by 6 publications

References 24 publications

Valid Presumption of Shiga Toxin-Mediated Damage of Developing Erythrocytes in EHEC-Associated Hemolytic Uremic Syndrome

Valid Presumption of Shiga Toxin-Mediated Damage of Developing Erythrocytes in EHEC-Associated Hemolytic Uremic Syndrome

Flow behavior of fetal, neonatal and adult RBCs in narrow (3–6 μm) capillaries – Calculation and experimental application

Red blood cell mechanical stability test

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