Specific proportions of sub lethally damaged red blood cells (RBCs) in an average dialysis treatment are difficult to quantify precisely, as the damage depends heavily on device design, flow conditions, and individual patient factors. However, research indicates that low-grade chronic damage is common, significantly shortening the average RBC lifespan from a normal of 100-120 days to as low as 58-65 days in dialysis patients. 

Key Details on Sublethal RBC Damage

• Impact of Shear Stress: While healthy RBCs are flexible and can withstand a wide range of physiological shear stresses, the non-physiological shear stress (NPSS) generated by medical devices like dialysis machines can cause sublethal injury.
• Mechanism of Damage: Sublethal damage involves changes to the cell membrane and cytoskeleton that do not immediately burst the cell (hemolysis) but make it more rigid and fragile. These rigidified cells are prematurely filtered and destroyed by the spleen, leading to chronic anemia.
• Thresholds: Sublethal damage can begin at shear stress levels around 21-43 Pa (210-430 dynes/cm²), which is within the range that can be encountered in extracorporeal circuits, while lethal damage (hemolysis) occurs at a much higher threshold of about 150 Pa (1500 dynes/cm²).
• Contributing Factors:
  • Device Design: Modern dialysis equipment and filters are generally designed to minimize damage, but factors like flow rates, needle dimensions, and surface coatings still play a role.
  • Patient Factors: Uremic erythrocytes are inherently less deformable than healthy ones, making them more susceptible to damage during the dialysis process.
  • Exposure Time: The duration of exposure to a specific shear stress is a critical factor; longer exposure to lower stress can be as damaging as brief exposure to high stress. 

In essence, while acute, massive damage (hemolysis) is rare with modern technology, a substantial cumulative amount of sublethal damage occurs over time, contributing significantly to the shortened RBC lifespan observed in hemodialysis patients. 

Low-grade chronic red blood cell (RBC) damage in dialysis significantly impairs perfusion and oxygen delivery to tissues, leading to chronic tissue hypoxia and microvascular dysfunction. 

The mechanisms by which this occurs include:

• Reduced Oxygen-Carrying Capacity: The primary effect of chronic RBC damage and the resulting anemia is a decreased ability of the blood to transport sufficient oxygen to tissues.
• Endothelial Dysfunction: The continuous, low-grade hemolysis releases cell-free hemoglobin into the bloodstream. This free hemoglobin scavenges nitric oxide (NO), a crucial molecule for vasodilation and healthy blood flow. The resulting NO depletion leads to vasoconstriction and endothelial dysfunction, directly impeding perfusion in the microcirculation.
• Microvascular Rarefaction: The uremic environment in patients with chronic kidney disease (CKD) and the effects of dialysis contribute to structural damage of the microvasculature, resulting in a loss of functional capillaries (microvascular rarefaction). This increases the diffusion distance for oxygen and nutrients from the remaining vessels to the tissue cells, further compromising oxygen supply.
• Decreased RBC Deformability: Uremic erythrocytes are less flexible and more fragile than normal RBCs. This reduced deformability can hinder their ability to navigate the smallest capillaries effectively, further impairing microcirculatory flow and oxygen delivery.
• Altered Hemoglobin-Oxygen Affinity: Hemodialysis can cause acute shifts in blood pH (Bohr effect), which can transiently increase the affinity of hemoglobin for oxygen. This means less oxygen is released to the peripheral tissues, exacerbating the problem of inadequate oxygen delivery. 

In essence, low-grade chronic red blood cell damage contributes to a vicious cycle of impaired oxygen transport and microvascular injury, which is a major factor in the progressive end-organ damage (e.g., in the heart and brain) and the high cardiovascular risk associated with end-stage renal disease.