Bile acid - independent flow _a._

salts k CO2

Conjugation with taurine or glycine

salts k CO2

Bile salt Cholesterol vPhospholipidV Bilirubin HCO3

Carbonic anhydrase

The mechanism of bile salt secretion and bile flow. (1) Na+/K+-ATPase. (2) Bile salt-sodium symport. (3) Canalicular bile salt carrier. (4) Na+/H4 exchanger. (5) HCO3~ transport system.

Canalicular Bile Acid-Dependent Flow. Hepatocyte uptake of free and conjugated bile salts is Na+ -dependent and mediated by bile salt-sodium symport (Fig. 27.15). The energy required is provided by the transmembrane Na+ gradient generated by the Na+/K.+ -ATPase. This mechanism is a type of secondary active transport because the energy required for the active uptake of bile acid, or its conjugate, is not directly provided by ATP but by an ionic gradient. The free bile acids are reconjugated with taurine or glycine before secretion. Hepatocytes also make new bile acids from cholesterol. Bile salts are secreted by hepa-tocytes by a carrier located at the canalicular membrane. This secretion is not Na+-dependent; instead, it is driven by the electrical potential difference between the hepato-cyte and the canaliculus lumen.

Other major components of bile, such as phospholipid and cholesterol, are secreted in concert with bile salts. Bilirubin is secreted by hepatocytes via an active process. Although the secretion of cholesterol and phospholipid is not well understood, it is closely coupled to bile salt secretion. The osmotic pressure generated as a result of the secretion of bile salts draws water into the canaliculus lumen through the paracellular pathway.

Canalicular Bile Acid-Independent Flow. As the name implies, this component of canalicular flow is not dependent on the secretion of bile acids (see Figs. 27.14 and 27.15). The Na+/K.+ -ATPase plays an important role in bile acid-independent bile flow, a role that is clearly demonstrated by the marked reduction in bile flow when an inhibitor of this enzyme is applied. Another mechanism responsible for bile acid-independent flow is canalicular HCO 3 secretion.

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Essentials of Human Physiology

Essentials of Human Physiology

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