Comprehensive Physiology Wiley Online Library

Hepatic Transport of Organic Solutes

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Functional Anatomy
1.1 Vascular Organization of Hepatic Parenchyma
1.2 Structural Adaptations for Efficient Solute Exchange Between Blood and Tissue
1.3 Liver Cell Plates, Canaliculi, and Tight Junctions
1.4 Intra‐Acinar Heterogeneity
2 Experimental Methods
3 Transport Mechanisms
3.1 Classification
3.2 Carrier‐Mediated Transport
3.3 Compartmentation of Solutes Inside Cell and in Bile
3.4 Effect of Choleresis on Canalicular Anion Transport
4 Mathematical Modeling
4.1 Steady‐State Input‐Output Relations
4.2 Distribution of Flow to Multiple Sinusoids
4.3 Estimating Uptake, Efflux, and Removal Separately
5 Uptake of Albumin‐Bound Organic Anions
5.1 Historical Perspective
5.2 Dissociation‐Mediating Sites on the Cell Surface?
5.3 Specificity
6 Transport of Specific Solute Classes
6.1 Bile Acids
6.2 Long‐Chain Fatty Acids
6.3 Other Organic Anions
6.4 Amino Acids
6.5 Organic Cations
6.6 Neutral Compounds
6.7 Intracellular Binding Proteins
6.8 Putative Membrane Carriers
7 Conclusion
Figure 1. Figure 1.

Parenchymal architecture. A: sinusoid; B: liver cell plate; C: hepatic venule; D: canaliculi; E: hepatic arteriole; F: bile ductule with peribiliary capillary plexus; G: portal venule; H: portal vein.

Adapted from Leevy 71a)
Figure 2. Figure 2.

Anatomy of sinusoidal solute exchange. A: sinusoid; B: lateral recess and junctional complex; C: canaliculus; D: Disse space; E: endothelial fenestrae.

Adapted from Leevy 71a)
Figure 3. Figure 3.

Reaction scheme for carrier‐mediated transport.

Figure 4. Figure 4.

A: entire liver lumped into two homogeneous compartments. B: distributed modeling of single sinusoid to account for changes in solute concentration with position.

Figure 5. Figure 5.

A: hepatic venous outflow curves simulated for Gaussian flow distributions with different variances. B: perfusate disappearance curves simulated for same sinusoidal flow distributions as in A.

From Forker and Luxon 32a)
Figure 6. Figure 6.

Removal of tracer rose bengal by perfused rat liver at various concentrations of bovine albumin. Observations appear as discrete points. Solid curve depicts relation predicted by assuming that only free rose bengal is available for hepatic uptake.

Figure 7. Figure 7.

Receptor model for surface‐mediated dissociation of albumin‐bound ligands. L, free ligand; A, free albumin; C, albumin‐ligand complex.



Figure 1.

Parenchymal architecture. A: sinusoid; B: liver cell plate; C: hepatic venule; D: canaliculi; E: hepatic arteriole; F: bile ductule with peribiliary capillary plexus; G: portal venule; H: portal vein.

Adapted from Leevy 71a)


Figure 2.

Anatomy of sinusoidal solute exchange. A: sinusoid; B: lateral recess and junctional complex; C: canaliculus; D: Disse space; E: endothelial fenestrae.

Adapted from Leevy 71a)


Figure 3.

Reaction scheme for carrier‐mediated transport.



Figure 4.

A: entire liver lumped into two homogeneous compartments. B: distributed modeling of single sinusoid to account for changes in solute concentration with position.



Figure 5.

A: hepatic venous outflow curves simulated for Gaussian flow distributions with different variances. B: perfusate disappearance curves simulated for same sinusoidal flow distributions as in A.

From Forker and Luxon 32a)


Figure 6.

Removal of tracer rose bengal by perfused rat liver at various concentrations of bovine albumin. Observations appear as discrete points. Solid curve depicts relation predicted by assuming that only free rose bengal is available for hepatic uptake.



Figure 7.

Receptor model for surface‐mediated dissociation of albumin‐bound ligands. L, free ligand; A, free albumin; C, albumin‐ligand complex.

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E. L. Forker. Hepatic Transport of Organic Solutes. Compr Physiol 2011, Supplement 18: Handbook of Physiology, The Gastrointestinal System, Salivary, Gastric, Pancreatic, and Hepatobiliary Secretion: 693-716. First published in print 1989. doi: 10.1002/cphy.cp060334