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KEY POINTS

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  • The liver’s strategic location between intestinal tract and the rest of the body facilitates its maintenance of metabolic homeostasis in the body.

  • The liver extracts ingested nutrients, vitamins, metals, drugs, environmental toxicants, and waste products of bacteria from the blood for catabolism, storage, and/or excretion into bile.

  • Formation of bile is essential for uptake of lipid nutrients from the small intestine, protection of the small intestine from oxidative insults, and excretion of endogenous and xenobiotic compounds.

  • Cholestasis is either a decrease in the volume of bile formed or an impaired secretion of specific solutes into bile, which results in elevated serum levels of bile salts and bilirubin.

  • Hepatocytes have a rich supply of phase I enzymes that often convert xenobiotics to reactive electrophilic metabolites and of phase II enzymes that add a polar group to a molecule and thereby enhance its removal from the body. The balance between phase I and phase II reactions determines whether a reactive metabolite will initiate liver cell injury or be safely detoxified.

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INTRODUCTION

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The liver is the main organ where exogenous chemicals are metabolized and eventually excreted. As a consequence, liver cells are exposed to significant concentrations of these chemicals, which can result in liver dysfunction, cell injury, and even organ failure. The liver, with its multiple cell types and numerous functions, can respond in many different ways to acute and chronic insults. To recognize potential liver cell dysfunction and injury, it is necessary to have a general knowledge of basic liver functions, the structural organization of the liver, the processes involved in hepatic excretory functions, and mechanisms of cell and organ injury.

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LIVER PHYSIOLOGY

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Hepatic Functions

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The liver’s strategic location between intestinal tract and the rest of the body facilitates the performance of its enormous task of maintaining the metabolic homeostasis of the body. Venous blood from the stomach and intestines flows into the portal vein, through the liver, and then enters the systemic circulation. The liver is the first organ to encounter ingested nutrients, vitamins, metals, drugs, and environmental toxicants as well as waste products of bacteria that enter portal blood. Efficient scavenging or uptake processes extract these absorbed materials from the blood for catabolism, storage, and/or excretion into bile.

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All of the major functions of the liver can be detrimentally altered by acute or chronic exposure to toxicants (Table 13–1). When toxicants inhibit or otherwise impede hepatic transport and synthetic processes, dysfunction can occur without appreciable cell damage. Loss of function also occurs when toxicants kill a considerable number of cells and when chronic insult leads to replacement of cell mass by nonfunctional scar tissue.

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Table Graphic Jump Location
TABLE 13–1

Major functions of liver and consequences of impaired hepatic functions.

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