Influence of microflow on hepatic sinusoid blood flow and red blood cell deformation.

Hepatic sinusoids present complex anatomical structures such as the endothelial sieve pores and the Disse space, which govern the microscopic blood flow in the sinusoids and are associated with structural variations in liver fibrosis and cirrhosis. However, the contributions of the permeability of endothelial and collagen layers and the roughness of hepatocyte microvilli to the features of this microflow remain largely unknown. Here, an immersed boundary method coupled with a lattice Boltzmann method was adopted in an in vitro hepatic sinusoidal model, and flow field and erythrocyte deformation analyses were conducted by introducing three new source terms including permeability of the endothelial layer, resistance of hepatocyte microvilli and collagen layers, and deformation of red blood cells (RBCs). Numerical calculations indicated that alterations in endothelial permeability could significantly affect the flow velocity and flow rate distributions in hepatic sinusoids. Interestingly, a biphasic regulating pattern of shear stress occurred simultaneously on the surface of hepatocytes and the lower side of endothelium, i.e., the shear stress increased with increased thickness of hepatocyte microvilli and collagen layer when the endothelial permeability was high but decreased with the increase of the thickness at low endothelial permeability. Additionally, this specified microflow manipulates typical RBC deformation inside the sinusoid, yielding one-third of the variation of deformable index with varied endothelial permeability. These simulations not only are consistent with experimental measurements using in vitro liver sinusoidal chip but also elaborate the contributions of endothelial and collagen layer permeability and wall roughness. Thus, our results provide a basis for further characterizing this microflow and understanding its effects on cellular migration and deformation in the hepatic sinusoids.

Biphasic flow dynamics and polarized mass transportation in branched hepatic sinusoids.

In fatty liver diseases, such as liver fibrosis and liver cirrhosis, blood flow in hepatic sinusoids, an elementary building block of the liver lobule, tends to bypass through collateral vessels inside sinusoids and presents distinct sinusoidal flows compared to normal physiological flows. It remains unclear in those flow characteristics in branched sinusoids and the correlation of pathological flows with liver lesions, mainly due to the difficulty of direct hemodynamics measurements in the sinusoids. Here, we developed a dual-branched theoretical model of hepatic sinusoidal flow to elucidate the relevant flow dynamics and mass transport. Numerical simulations, based on the lattice Boltzmann method, indicated that the flow velocity distribution in hepatic sinusoids is mainly dominated by endothelium permeability and presents a non-monotonic variation with the permeability at the fusion segment of these branched sinusoids. Flow-induced shear stress on the endothelium at the side of the Disse space exhibited a biphasic pattern, yielding a low shear stress region at the junctional site. Meanwhile, a highly polarized distribution of lipoproteins concentration was also presented at the low shear stress region, indicating a localized accumulation of typical hepatic serum proteins. Thus, this work provides the basic understanding of blood flow features and mass transport regulations in branched hepatic sinusoids.