The liver is a metabolically complex organ. Hepatocytes (liver parenchymal cells) perform the liver’s metabolic functions:
Formation and excretion of bile as a component of bilirubin metabolism (see Overview of bilirubin metabolism Overview of bilirubin metabolism The liver is a metabolically complex organ. Hepatocytes (liver parenchymal cells) perform the liver’s metabolic functions: Formation and excretion of bile as a component of bilirubin metabolism... read more )
Control of cholesterol metabolism
Formation of urea, serum albumin, clotting factors, enzymes, and numerous other proteins
Overview of liver structure
At the cellular level, portal triads consist of adjacent and parallel terminal branches of bile ducts, portal veins, and hepatic arteries that border the hepatocytes. Terminal branches of the hepatic veins are in the center of hepatic lobules. Blood flows from the portal triads past the hepatocytes and drains via vein branches in the center of the lobule, rendering the center of the lobule the area most susceptible to ischemia.
Organization of the liver
The liver is organized into lobules around terminal branches of the hepatic vein (central veins). Between the lobules are portal triads. Each triad consists of branches of a bile duct, portal vein, and hepatic artery.
Overview of bilirubin metabolism
The breakdown of hemoglobin produces bilirubin (an insoluble waste product) and other bile pigments. Bilirubin must be made water soluble to be excreted. This transformation occurs in 5 steps: formation, plasma transport, liver uptake, conjugation, and biliary excretion.
Formation: About 250 to 350 mg of unconjugated bilirubin forms daily; 70 to 80% derives from the breakdown of degenerating red blood cells, and 20 to 30% (early-labeled bilirubin) derives primarily from other heme proteins in the bone marrow and liver. Hemoglobin is degraded to iron and biliverdin, which is converted to bilirubin.
Plasma transport: Unconjugated (indirect-reacting) bilirubin is not water soluble and so is transported in the plasma bound to albumin. It cannot pass through the glomerular membrane into the urine. Albumin binding weakens under certain conditions (eg, acidosis), and some substances (eg, salicylates, certain antibiotics) compete for the binding sites.
Liver uptake: The liver takes up bilirubin rapidly but does not take up the attached serum albumin.
Conjugation: Unconjugated bilirubin in the liver is conjugated to form mainly bilirubin diglucuronide (conjugated [direct-reacting] bilirubin). This reaction, catalyzed by the microsomal enzyme glucuronyl transferase, renders the bilirubin water soluble.
Biliary excretion: Tiny canaliculi formed by adjacent hepatocytes progressively coalesce into ductules, interlobular bile ducts, and larger hepatic ducts. Outside the porta hepatis, the main hepatic duct joins the cystic duct from the gallbladder to form the common bile duct, which drains into the duodenum at the ampulla of Vater.
Conjugated bilirubin is secreted into the bile canaliculus with other bile constituents. In the intestine, bacteria metabolize bilirubin to form urobilinogen, much of which is further metabolized to stercobilins, which render the stool brown. In complete biliary obstruction, stools lose their normal color and become light gray (clay-colored stool). Some urobilinogen is reabsorbed, extracted by hepatocytes, and re-excreted in bile (enterohepatic circulation). A small amount is excreted in urine.
Because conjugated bilirubin is excreted in urine and unconjugated bilirubin is not, only conjugated hyperbilirubinemia (eg, due to hepatocellular or cholestatic jaundice) causes bilirubinuria.
Pathophysiology of Liver Disorders
Liver disorders can result from a wide variety of insults, including infections, drugs, toxins, ischemia, and autoimmune disorders. Occasionally, liver disorders occur postoperatively Postoperative Liver Dysfunction Mild liver dysfunction sometimes occurs after major surgery even in the absence of preexisting liver disorders. This dysfunction usually results from hepatic ischemia or poorly understood effects... read more . Most liver disorders cause some degree of hepatocellular injury and necrosis, resulting in various abnormal laboratory test results and, sometimes, symptoms. Symptoms may be due to liver disease itself (eg, jaundice Jaundice Jaundice is a yellowish discoloration of the skin and mucous membranes caused by hyperbilirubinemia. Jaundice becomes visible when the bilirubin level is about 2 to 3 mg/dL (34 to 51 micromol/L)... read more due to acute hepatitis) or to complications of liver disease (eg, acute gastrointestinal bleeding due to cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense... read more and portal hypertension Portal Hypertension Portal hypertension is elevated pressure in the portal vein. It is caused most often by cirrhosis (in North America), schistosomiasis (in endemic areas), or hepatic vascular abnormalities. Consequences... read more ).
Despite necrosis, the liver can regenerate itself. Even extensive necrosis can resolve completely (eg, in acute viral hepatitis). Incomplete regeneration and fibrosis Hepatic Fibrosis Hepatic fibrosis is overly exuberant wound healing in which excessive connective tissue builds up in the liver. The extracellular matrix is overproduced, degraded deficiently, or both. The trigger... read more , however, may result from injury that bridges entire lobules or from less pronounced but ongoing damage.
Specific diseases preferentially affect certain hepatobiliary structures or functions (eg, acute viral hepatitis Overview of Acute Viral Hepatitis Acute viral hepatitis is diffuse liver inflammation caused by specific hepatotropic viruses that have diverse modes of transmission and epidemiologies. A nonspecific viral prodrome is followed... read more is primarily manifested by damage to hepatocytes or hepatocellular injury; primary biliary cholangitis Primary Biliary Cholangitis (PBC) Primary biliary cholangitis (PBC; formerly known as primary biliary cirrhosis) is an autoimmune liver disorder characterized by the progressive destruction of intrahepatic bile ducts, leading... read more , by impairment of biliary secretion; and cirrhosis, by liver fibrosis and resultant portal venous hypertension). The part of the hepatobiliary system affected determines the symptoms, signs, and laboratory abnormalities (see testing for hepatic and biliary disorders Laboratory Tests of the Liver and Gallbladder Laboratory tests are generally effective for the following: Detecting hepatic dysfunction Assessing the severity of liver injury Monitoring the course of liver diseases and the response to treatment... read more ). Some disorders (eg, severe alcohol-related liver disease Alcohol-Related Liver Disease Alcohol consumption is high in most Western countries. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), 8.5% of US adults are estimated to... read more ) affect multiple liver structures, resulting in a combination of patterns of symptoms, signs, and laboratory abnormalities.
The prognosis of serious complications is worse in older adults, who are less able to recover from severe physiologic stresses and to tolerate toxic accumulations.