Physical Properties of Blood and their Relationship to Clinical Conditions

Abstract

It has been long known that blood health heavily influences optimal physiological function. Abnormalities affecting the physical properties of blood have been implicated in the pathogenesis of various disorders, although the exact mechanistic links between hemorheology and clinical disease manifestations remain poorly understood. Often overlooked in current medical practice, perhaps due to the promises offered in the molecular and genetic era, the physical properties of blood which remain a valuable and definitive indicator of circulatory health and disease. Bridging this gap, the current manuscript provides an introduction to hemorheology. It reviews the properties that dictate bulk and microcirculatory flow by systematically dissecting the biomechanics that determine the non-Newtonian behavior of blood. Specifically, the impact of hematocrit, the mechanical properties and tendency of red blood cells to aggregate, and various plasma factors on blood viscosity will be examined. Subsequently, the manner in which the physical properties of blood influence hemodynamics in health and disease is discussed. Special attention is given to disorders such as sickle cell disease, emphasizing the clinical impact of severely abnormal blood rheology. This review expands into concepts that are highly topical; the relation between mechanical stress and intracellular homeostasis is examined through a contemporary cell-signaling lens. Indeed, accumulating evidence demonstrates that nitric oxide is not only transported by erythrocytes, but is locally produced by mechanically-sensitive enzymes, which appears to have intracellular and potentially extracellular effects. Finally, given the importance of shear forces in the developing field of mechanical circulatory support, we review the role of blood rheology in temporary and durable mechanical circulatory support devices, an increasingly utilized method of life support. This review thus provides a comprehensive overview for interested trainees, scientists, and clinicians.

Keywords: aggregation; blood viscosity; deformability; hemorheology; medical devices.

FIGURE 1

Blood is a shear-thinning fluid, where it is most thick within the venous network with lower shear and it becomes progressively thinner under the higher shear regions of the arterial network and microcirculation. The tendency for RBC to cluster (i.e., aggregate; micrograph) is the primary determinant of blood viscosity at low shear, and the dispersion of these clusters aids in dramatically decreasing blood viscosity with increasing shear. The shear thinning observed at >100 s⁻¹ may be attributed to the unique capacity of RBC to deform from their resting discocyte shape to hydrodynamically favorable morphologies, thus reducing the internal resistance of blood.

FIGURE 2

The figure demonstrates some of the complex interactions between cellular mechanics of red blood cells (RBC), the flux of the microcirculation, and intracellular signaling within these cells. Under healthy conditions, RBC are highly deformable, which enables them to migrate to the center of flow thereby creating a cell-poor layer (A) and to pass easily throughout daughter branches of the microcirculation. Less deformable RBC (B), however, tend to have greater heterogeneity of distribution within larger vessels, resulting in a much narrower cell-poor layer and thus greater wall shear stress. Upon reaching bifurcations, these rigid RBC are unable to enter smaller capillaries, prompting a maldistribution of RBC and impaired flux of these pathways. Other mechanisms are also of critical importance, such as hypoxic vasodilation, yet not shown on this figure.

FIGURE 3

The clinical outcomes for those suffering from rheological disturbances have seemingly diverse, although clearly interconnected pathogeneses. Irrespective of the cause, the impact of perturbed blood rheological properties tend to impair blood flow at both the macro- and microcirculatory scale.