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After studying this chapter, you should be able to:

  • Understand the functional anatomy of the liver and the relative arrangements of hepatocytes, cholangiocytes, endothelial cells, and Kupffer cells.

  • Define the characteristics of the hepatic circulation and its role in subserving the liver’s functions.

  • Describe the major functions of the liver with respect to metabolism, detoxification, and excretion of hydrophobic substances.

  • Identify the plasma proteins that are synthesized by the liver.

  • Outline the mechanisms by which the liver contributes to whole body ammonia homeostasis and the consequences of the failure of these mechanisms, particularly for brain function.

  • Describe the constituents of bile, its formation, and its role in the excretion of cholesterol and bilirubin.

  • Identify the mechanisms that permit normal functioning of the gallbladder and the basis of gallstone disease.


The liver is the largest gland in the body. It is essential for life because it conducts a vast array of biochemical and metabolic functions, including ridding the body of substances that would otherwise be injurious if allowed to accumulate, and excreting drug metabolites. It is also the first port of call for most nutrients absorbed across the gut wall, supplies most of the plasma proteins, and synthesizes the bile that optimizes the absorption of fats as well as serving as an excretory fluid. The liver and associated biliary system have therefore evolved an array of structural and physiologic features that underpin this broad range of critical functions.



An important function of the liver is to serve as a filter between the blood coming from the gastrointestinal tract and the blood in the rest of the body. Blood from the intestines and other viscera reach the liver via the portal vein. This blood percolates in sinusoids between plates of hepatic cells and eventually drains into the hepatic veins, which in turn empty into the inferior vena cava. Hepatic artery blood also enters the sinusoids. During its passage through the hepatic plates, the blood is extensively modified chemically. Bile is formed on the other side of each plate (Figure 28–1).


Schematic anatomy of the liver. Hepatocytes are arranged radially in plates surrounding a central vein. Blood is supplied to the liver by branches of the portal vein (PV) and hepatic artery (HA), which empty into sinusoids (S) surrounding the hepatocytes. The direction of blood flow is indicated with black arrows. The endothelial cells that line the sinusoids are fenestrated and thus provide little hindrance to the transfer of substances from the sinusoids to the space of Disse, which abuts the basolateral membrane of the hepatocytes. The apical membranes of adjacent hepatocytes form bile canaliculi, which transfer bile to the bile ducts lined by cholangiocytes. Bile flows in the opposite direction to blood (green arrows). The bile duct, portal vein, ...

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