The liver is located in the abdominal cavity and receives portal blood from the stomach, small and large intestines, pancreas, and spleen. The functions of the liver include processing of absorbed substances; synthesis and secretion of bile acids; bilirubin production and excretion; participation in metabolism of key nutrients including carbohydrates, proteins, and lipids; and detoxification and excretion of waste products.
The majority of the liver’s blood supply is venous blood from the gastrointestinal tract (spleen, stomach, small and large intestines, and pancreas), which is delivered to the liver via the portal vein, as shown inFigure 8-37. Therefore, the liver is ideally located to receive absorbed nutrients and to detoxify absorbed substances that may be harmful such as drugs and toxins.
Figure 8–37 Blood flow in the splanchnic circulation.
Bile Formation and Secretion
As already described (see Bile Secretion), bile acids are synthesized from cholesterol by the hepatocytes, transported into the bile, stored and concentrated in the gallbladder, and secreted into the intestinal lumen to aid in the digestion and absorption of dietary lipids. Bile acids are then recirculated from the ileum back to the liver via the enterohepatic circulation.
Bilirubin Production and Excretion
The reticuloendothelial system (RES) processes senescent red blood cells (Fig. 8-38). When hemoglobin is degraded by the RES, one of the byproducts is biliverdin (green-colored), which is converted tobilirubin (yellow-colored). Bilirubin is then bound to albumin in the circulation and carried to the liver, where it is taken up by the hepatocytes. In hepatic microsomes, bilirubin is conjugated with glucuronic acid via the enzyme UDP glucuronyl transferase.(Because UDP glucuronyl transferase is synthesized slowly after birth, some newborn babies develop “newborn jaundice.”) Conjugated bilirubin is water soluble, and a portion of it is excreted in the urine. The remainder of the conjugated bilirubin is secreted into bile and then, via bile, into the small intestine. The conjugated bilirubin travels down to the terminal ileum and colon, where it is deconjugated by bacterial enzymes and metabolized to urobilinogen, some of which is absorbed via the enterohepatic circulation and delivered back to the liver; the remainder is converted to urobilin and stercobilin, which are excreted in the feces.
Figure 8–38 Bilirubin metabolism. UDP, uridine diphosphate.
Jaundice is a yellow discoloration of the skin and sclera of the eyes due to accumulation of either free or conjugated bilirubin. Jaundice can occur when there is increased destruction of red blood cells that results in increased production of unconjugated bilirubin. Jaundice also occurs with obstruction of bile ducts or with liver disease; in these cases, conjugated bilirubin cannot be excreted in the bile and thus is absorbed into the circulation. In obstructive jaundice, the urine is dark, owing to the high urinary concentration of conjugated bilirubin, and the stool is light (“clay-colored”), owing to the decreased amount of fecal stercobilin.
Metabolic Functions of the Liver
The liver participates in the metabolism of carbohydrates, proteins, and lipids. In carbohydrate metabolism, the liver performs gluconeogenesis, stores glucose as glycogen, and releases stored glucose into the bloodstream, when needed.
In protein metabolism, the liver synthesizes the nonessential amino acids and modifies amino acids so that they may enter biosynthetic pathways for carbohydrates. The liver also synthesizes almost all plasma proteins including albumin and the clotting factors. Persons with liver failure develop hypoalbuminemia (which may lead to edema due to loss of plasma protein oncotic pressure) and clotting disorders. The liver also converts ammonia, a byproduct of protein catabolism, to urea, which is then excreted in the urine.
In lipid metabolism, the liver participates in fatty acid oxidation and synthesizes lipoproteins, cholesterol, and phospholipids. As previously described, the liver converts a portion of the cholesterol to bile acids, which participate in lipid digestion and absorption.
Detoxification of Substances
The liver protects the body from potentially toxic substances that are absorbed from the GI tract. These substances are presented to the liver via the portal circulation, and the liver modifies them in so-called “first pass metabolism,” ensuring that little or none of the substances make it into the systemic circulation. For example, bacteria absorbed from the colon are phagocytized by hepatic Kupffer cells and thus never enter the systemic circulation. In another example, liver enzymes modify both endogenous and exogenous toxins to render them water soluble and thus capable of being excreted in either bile or urine.Phase I reactions, which are catalyzed by cytochrome P-450 enzymes, are followed by phase II reactions that conjugate the substances with glucuronide, sulfate, amino acids, or glutathione.