Seminar, 20. November 2014, Ole Schwen

20. November 2014, 16:00
Ernst-Abbe-Platz 2, seminar room 3423

Multi-scale simulation of heterogeneous metabolism in mammalian livers

Dr. Lars Ole Schwen
(Fraunhofer MEVIS, Bremen)

One of the manifold tasks of the liver in the mammalian body is the detoxification of blood, i.e., the removal of foreign and potentially harmful compounds from the circulating blood. This work is performed mainly by hepatocytes, liver cells that are organized along sinusoids (capillaries) where they exchange compounds with the blood flowing past.

This metabolization may be performed differently by hepatocytes at different positions in the liver or along the sinusoids. Already in healthy livers, zonated cellular properties like the presence of enzymes may lead to different metabolization properties. In case of diseases, the hepatocytes can be affected according to a zonated pattern. Other scales of heterogeneity occur if different regions of the liver are affected to a different extent.

Based on physiologically based pharmacokinetics (PBPK) models, we show two different multi-scale perfusion and metabolization modeling frameworks. In one approach, the liver tissue is represented as a porous medium, in which a multi-phase 3D advection-reaction equation is solved. In a second approach, we introduce an additional scale denoted by representative sinusoids, each of which stands for one region of the liver with essentially the same zonation of metabolization parameters. In this case, we solve a 1D advection-reaction equation.

We present several example applications using these two modeling approaches, both for healthy and for diseased livers. Steatosis, a common disease resulting in the formation of abnormal lipid accumulations in the cells, can be observed to be heterogeneous both at the sinusoidal and at larger length scales. Besides synthetic data for the diseased states, we also present one simulation of the caffeine metabolism in steatotic mouse livers for which the zonated and heterogeneous steatosis was quantified based on a histological slice of a mouse liver.