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Zonal diversity or zonal heterogeneity in bile secretion
1230
CORRESPONDENCE
GASTROENTEROLOGY
2. Lake-Bakaar G, Quadros E, Beidas S, et al. Gastric secretory failure in patients with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1988;109:502-4. 3. Andersen LP. Invading Campylobacter pylori? Gastroduodenal pathology and Campylobacter pylori. European Campylobacter pylori study group, Bordeaux, France. October 1988. p. 105.
Zonal Diversity Bile Secretion
or Zonal Heterogeneity
in
Dear Sir: In a recent review article by Traber et al. (1).the authors discussed several areas of liver function, including bile secretion. in which they claimed zonal “heterogeneity” in hepatocytes has been established. The objective of this letter is to discuss whether there is heterogeneity in bile secretion in light of the proposal presented in this review. The authors’ proposal is well summarized in their Figure 4. Hepatocytes of zone 1 contribute predominantly to the secretion of bile salt-dependent bile flow (BSDF); however, hepatocytes of zone 3 actively (and in another part of the text, “predominantly”) contribute to the formation of bile salt-independent bile flow (BSIF) in the physiologic state. “Heterogeneity” as defined by the English dictionary is “a condition of being composed of diverse qualitative constituents;” therefore this word cannot be correctly used to describe quantitative differences in bile formation between the acinus zones. In addition, the authors pointed out that there are no quantitative differences in bile acid uptake and that the taurocholate uptake system appears to be equally distributed through the hepatocytes of the liver acinus. This suggests that the predominant zonal location of bile salt transport within the acinus is due to availability of bile salts and not to intrinsic zonal “heterogeneity” in the capability of bile salt uptake, or the secretion of BSDF. The authors further suggested in Figure 4 that in physiologic conditions in the rat, hepatocytes of zone 3 receive a lower load of bile salts than hepatocytes of zones 1 and 2, but as these hepatocytes participate in bile flow, their contribution to bile flow is mainly bile salt-independent. This does not mean that hepatocytes of zones 1 and 2 do not contribute to BSIF and. in fact, the authors admit that the contribution of zones 1 and 3 to total secretion of BSIF is unknown. Thus, it is premature to imply in the figure that zones 1 and 2 produce less BSIF than zone 3. In fact. there is evidence to suggest that all hepatocytes in the acinus contribute to BSIF to the same extent. First, BSIF in the rat does not depend on bile salt secretion in physiologic conditions. Second, assuming BSIF in rat bile is 60% of total bile flow (2), and assuming that bromobenzene treatment in the authors’ previous work damaged 30% of the acinus, mainly zone 3, and this resulted in a 25% reduction in total bile flow, it can be calculated that zones 1 and 2 produced two-thirds of the BSIF. The authors’ previous observation of higher bile salt concentration in the bile produced after bromobenzene treatment, which implied that zone 3 provided fluid that dilutes the solutes secreted by zones 1 and 2. was never confirmed (3). In this laboratory, we actually obtained the opposite results (4). Finally, the study of Layden and Boyer (5). in which they showed a lobular gradient in canalicular size with that of centrolobular regions [zone 3) smaller (0.14 pm) than periportal regions (zone l), in physiologic conditions, but similar sizes after the infusion of taurocholate or dehydrocholate, suggests that no more than 20% of canalicular volume in zone 1 is due to bile salt secretion or BSDF, assuming a relationship between bile flow and canalicular volume in physiologic conditions. In conclusion, we may suggest that there is no “heterogeneity” between the hepatocytes in liver acinus in bile formation in rats
Vol. 96, No. 4
but rather there may be a zonal diversity in their contribution to bile formation that may be related to the availability of bile salts. IBRAHIMM.YOUSEF SERGE DIONNE GABRIELPLAA Department of Pharmacology Beatrize TuchL
CORRESPONDENCE
GASTROENTEROLOGY
2. Lake-Bakaar G, Quadros E, Beidas S, et al. Gastric secretory failure in patients with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1988;109:502-4. 3. Andersen LP. Invading Campylobacter pylori? Gastroduodenal pathology and Campylobacter pylori. European Campylobacter pylori study group, Bordeaux, France. October 1988. p. 105.
Zonal Diversity Bile Secretion
or Zonal Heterogeneity
in
Dear Sir: In a recent review article by Traber et al. (1).the authors discussed several areas of liver function, including bile secretion. in which they claimed zonal “heterogeneity” in hepatocytes has been established. The objective of this letter is to discuss whether there is heterogeneity in bile secretion in light of the proposal presented in this review. The authors’ proposal is well summarized in their Figure 4. Hepatocytes of zone 1 contribute predominantly to the secretion of bile salt-dependent bile flow (BSDF); however, hepatocytes of zone 3 actively (and in another part of the text, “predominantly”) contribute to the formation of bile salt-independent bile flow (BSIF) in the physiologic state. “Heterogeneity” as defined by the English dictionary is “a condition of being composed of diverse qualitative constituents;” therefore this word cannot be correctly used to describe quantitative differences in bile formation between the acinus zones. In addition, the authors pointed out that there are no quantitative differences in bile acid uptake and that the taurocholate uptake system appears to be equally distributed through the hepatocytes of the liver acinus. This suggests that the predominant zonal location of bile salt transport within the acinus is due to availability of bile salts and not to intrinsic zonal “heterogeneity” in the capability of bile salt uptake, or the secretion of BSDF. The authors further suggested in Figure 4 that in physiologic conditions in the rat, hepatocytes of zone 3 receive a lower load of bile salts than hepatocytes of zones 1 and 2, but as these hepatocytes participate in bile flow, their contribution to bile flow is mainly bile salt-independent. This does not mean that hepatocytes of zones 1 and 2 do not contribute to BSIF and. in fact, the authors admit that the contribution of zones 1 and 3 to total secretion of BSIF is unknown. Thus, it is premature to imply in the figure that zones 1 and 2 produce less BSIF than zone 3. In fact. there is evidence to suggest that all hepatocytes in the acinus contribute to BSIF to the same extent. First, BSIF in the rat does not depend on bile salt secretion in physiologic conditions. Second, assuming BSIF in rat bile is 60% of total bile flow (2), and assuming that bromobenzene treatment in the authors’ previous work damaged 30% of the acinus, mainly zone 3, and this resulted in a 25% reduction in total bile flow, it can be calculated that zones 1 and 2 produced two-thirds of the BSIF. The authors’ previous observation of higher bile salt concentration in the bile produced after bromobenzene treatment, which implied that zone 3 provided fluid that dilutes the solutes secreted by zones 1 and 2. was never confirmed (3). In this laboratory, we actually obtained the opposite results (4). Finally, the study of Layden and Boyer (5). in which they showed a lobular gradient in canalicular size with that of centrolobular regions [zone 3) smaller (0.14 pm) than periportal regions (zone l), in physiologic conditions, but similar sizes after the infusion of taurocholate or dehydrocholate, suggests that no more than 20% of canalicular volume in zone 1 is due to bile salt secretion or BSDF, assuming a relationship between bile flow and canalicular volume in physiologic conditions. In conclusion, we may suggest that there is no “heterogeneity” between the hepatocytes in liver acinus in bile formation in rats
Vol. 96, No. 4
but rather there may be a zonal diversity in their contribution to bile formation that may be related to the availability of bile salts. IBRAHIMM.YOUSEF SERGE DIONNE GABRIELPLAA Department of Pharmacology Beatrize TuchL