Zonal liver cell heterogeneity : effects of oxygen on metabolic functions of hepatocytes

The morphology and function of hepatocytes are known to vary with position along the liver sinusoids from the portal triad to the central vein. Functions such as urea synthesis and the activity of the cytochrome P-450 system are different, depending on whether the cell is located in a peri-portal zone or in a peri-venous zone. The factors determining this heterogeneous function are not fully understood. Possible explanations of this phenomenon include gradients in hormones, substrates, oxygen, pH, innervation and extracellular matrix composition. Past studies are reviewed, and some recent efforts are described that examine the potential role of oxygen in directly or indirectly inducing differences in hepatocyte function. Partial pressure of oxygen appears to have a role in urea synthesis, lipid metabolism, cytochrome P-450 activity and gluco-neogenesis, which corresponds to in vivo zonal localisation of these functions. Thus, as part of the overall design criteria for a bio-artificial liver device, oxygen distribution at the tissue surface should be included with the more standard criteria, such as optimisation of flow rate, cell dispersal and cell density within these systems. Keywords—Bio-artificial liver, Hepatocyte, Heterogeneity, Oxygen Cel l . Eng., 1996,1 , 125-135