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In Vivo Volume and Hemoglobin Dynamics of Human Red Blood Cells | PLOS Computational Biology

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Author Summary Red blood cell concentration (RBC), mean volume (MCV), and hemoglobin content (MCH) are routinely measured in the complete blood count, a fundamental clinical test essential for the screening, diagnosis, and management of most diseases. Variation in MCV and MCH is associated with many important clinical conditions, but we do not understand the mechanisms controlling these red blood cell physical characteristics. Vesicle shedding is thought to be most important, but we show here that a dominant role for vesicle shedding violates empirical geometric and biophysical constraints. An additional unknown process must be primarily responsible. We show that this important unknown process must be coupled to changes in RBC surface area, and we quantify the magnitude of its effects.

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Human red blood cells (RBCs) lose ∼30% of their volume and ∼20% of their hemoglobin (Hb) content during their ∼100-day lifespan in the bloodstream. These observations are well-documented, but the mechanisms for these volume and hemoglobin loss events are not clear. RBCs shed hemoglobin-containing vesicles during their life in the circulation, and this process is thought to dominate the changes in the RBC physical characteristics occurring during maturation. We combine theory with single-cell measurements to investigate the impact of vesiculation on the reduction in volume, Hb mass, and membrane. We show that vesicle shedding alone is sufficient to explain membrane losses but not volume or Hb losses. We use dry mass measurements of human RBCs to validate the models and to propose that additional unknown mechanisms control volume and Hb reduction and are responsible for ∼90% of the observed reduction. RBC population characteristics are used in the clinic to monitor and diagnose a wide range of conditions including malnutrition, inflammation, and cancer. Quantitative characterization of cellular maturation processes may help in the early detection of clinical conditions where maturation patterns are altered.

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Vesicles,Hemoglobin,Reticulocytes,Molting,Radii,Red blood cells,Biophysics,Cell membranes

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https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003839

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In Vivo Volume and Hemoglobin Dynamics of Human Red Blood Cells

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Author Summary Red blood cell concentration (RBC), mean volume (MCV), and hemoglobin content (MCH) are routinely measured in the complete blood count, a fundamental clinical test essential for the screening, diagnosis, and management of most diseases. Variation in MCV and MCH is associated with many important clinical conditions, but we do not understand the mechanisms controlling these red blood cell physical characteristics. Vesicle shedding is thought to be most important, but we show here that a dominant role for vesicle shedding violates empirical geometric and biophysical constraints. An additional unknown process must be primarily responsible. We show that this important unknown process must be coupled to changes in RBC surface area, and we quantify the magnitude of its effects.

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https://journals.plos.org/ploscompbiol/article/figure/image?id=10.1371/journal.pcbi.1003839.g007&size=inline

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In Vivo Volume and Hemoglobin Dynamics of Human Red Blood Cells

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In Vivo Volume and Hemoglobin Dynamics of Human Red Blood Cells

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