Anemia in sepsis: the importance of red blood cell membrane changes (1)
Septic patients have the increased uptake of altered RBCs by the reticuloendothelial system. Indeed, alterations in RBC membrane composition and morphology, such as seen during the senescence process, can trigger RBC uptake by macrophages of the spleen and/or the liver.
The human RBC adopts a biconcave‐discoid shape in vivo. This shape represents an equilibrium between two opposite extremes of shape: the stomatocyte (membrane internalization) and the echinocyte (membrane externalization with formation of multiple spikes on the RBC surface).
The RBC membrane is composed of proteins (52% in weight), lipids (40%) and carbohydrates (8%). Lipids, including phospholipids, glycolipids and cholesterol, are arranged as a bilayer and distributed unevenly between the two leaflets of this bilayer, giving a transverse membrane asymmetry. Lipids, including phospholipids, glycolipids and cholesterol, are arranged as a bilayer and distributed unevenly between the two leaflets of this bilayer, giving a transverse membrane asymmetry.
Sepsis is a complex pathophysiological process that involves alterations in the microcirculation (vessels with a diameter <100 µm) and changes in the biochemical and physiological characteristics of the blood constituents. Sepsis can alter RBC morphology and rheology (viscosity, aggregation and deformability), and these alterations are likely to contribute to the microvascular changes in these patients.
The changes in RBC morphology in sepsis was reported. An increased number of abnormal RBCs, including echinocytic and spheroechynocytic transformations, associated with an increased aggregation process.
Reactive oxygen species (ROS) , which include superoxide anion (O2‐), hydroxyl radical (OH‐) and hydrogen peroxide (H2O2), produced by the WBCs can also damage hemoglobin and induce hemolysis. Binding of endotoxin (lipopolysaccharide, LPS) to the RBC membrane could play a role in the alterations in RBC rheology, although data on this effect are conflicting. Washed RBCs suspended in phosphate buffered saline showed no change in deformability after incubation with LPS, whereas RBCs incubated with LPS in whole blood exhibited markedly altered deformability. These results underline the important role of the activation of leukocytes with generation of cytokines and ROS, which can alter the RBC membrane.
In iso‐osmolality, biconcave RBCs from volunteers appear essentially as two populations of cells, and the forward light scatter channel histograms show a typically bimodal distribution of RBCs. On this histogram, it is possible to calculate the second moment of Dissymmetry of Pearson (PCD; 3 × (mean‐median)/σ), which expresses the sphericity of the RBC
In a mouse model of septic shock induced by cecal ligature and puncture, an increased B3/α spectrin ratio suggested a possible alteration of the membrane integral/peripheral ratio. These observations need confirmation in humans, as there are interspecies differences in RBC shape, membrane composition and rheology.
Altered RBCs are more rapidly cleared from the circulation. First, the SA content of the RBC membrane plays an essential role in RBC survival. In rats, more than 70% of neuraminidase‐treated injected RBCs disappeared from the circulating blood in 30 minutes compared with less than 2% of normal RBCs.