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Computational and Mathematical Methods in Medicine
Volume 2011, Article ID 185845, 8 pages
Research Article

Inbuilt Mechanisms for Overcoming Functional Problems Inherent in Hepatic Microlobular Structure

1Centre for Diabetes, Bart's and The London School of Medicine and Dentistry, Blizard Institute for Cell and Molecular Sciences, Queen Mary University of London, Newark Street, London E1 2AT, UK
2Department of Cellular Pathology, Bart's and The London NHS Trust, 80 Newark Street, London E1 2AT, UK
3Medical Engineering Division, The School of Engineering and Materials Science, Queen Mary University of London, Mile End, London E1 4NS, UK

Received 14 November 2010; Accepted 26 January 2011

Academic Editor: Edelmira Valero

Copyright © 2011 Robert D. Cohen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The spherical anatomy of human and rat liver lobules implies that more central cells have less time to carry out their function than more peripherally located cells because blood flows past them more rapidly. This problem could be overcome if more centrilobular cells could operate at higher temperatures than periportal cells. This study presents evidence for such a temperature gradient. Firstly, we use mathematical modelling to demonstrate that temperature increases towards the centre of the lobule. Secondly, we examine the distribution of a heat-generating protein and of a heat-sensitive protein across the rat and human liver lobules. Double-antibody staining of healthy liver from rat and human was used for visual scoring and for automated histomorphometric quantitation of the localisation of uncoupling protein-2 (known to generate heat) and of the transient receptor potential-v4 protein (known as a highly temperature-sensitive membrane protein). Both these proteins were found to be located predominantly in the centrilobular region of liver lobules. These findings support the suggestion that temperature gradients across the liver lobule may have evolved as a solution to the problem of reduced contact time between blood and cells at the centre as compared to the periphery of mammalian liver lobules.