Letter to the Editor and Comments on: Intravital dynamic and correlative imaging reveals diffusion-dominated canalicular and flow-augmented ductular bile flux

TL;DR

This paper critiques a recent study on bile flow mechanisms, emphasizing that current evidence supports osmotic flow in bile canaliculi rather than diffusion-dominated processes, and clarifies misconceptions for clinical relevance.

Contribution

It provides a detailed critique of the diffusion-dominated bile flux model, reaffirming the osmotic flow mechanism supported by previous quantitative studies.

Findings

Reaffirms osmotic water influx as primary bile transport mechanism

Challenges the diffusion-dominated flux model proposed by Vartak et al.

Clarifies potential clinical implications of bile flow understanding.

Abstract

Bile, the central metabolic product of the liver, is secreted by hepatocytes into bile canaliculi (BC), tubular subcellular structures of 0.5-2 $\mu$m diameter which are formed by the apical membranes of juxtaposed hepatocytes. BC interconnect to build a highly ramified 3D network that collects and transports bile towards larger interlobular bile ducts (IBD). The transport mechanism of bile is of fundamental interest and the current text-book model of "osmotic canalicular bile flow", i.e. enforced by osmotic water influx, has recently been quantitatively verified based on flux measurements and BC contractility (Meyer et al., 2017) but challenged in the article entitled "Intravital dynamic and correlative imaging reveals diffusion-dominated canalicular and flow-augmented ductular bile flux" (Vartak et al., 2020). We feel compelled to share a series of arguments that question the key conclusions of this study (Vartak et al., 2020), particularly because it risks to be misinterpreted and misleading for the field in view of potential clinical applications. We summarized the arguments in the following 8 points.