15. Jaundice / L.J. Scully 

A state characterized by increased serum bilirubin levels and a yellow appearance due to deposition of bile pigment in the skin and mucus membranes. 

Bilirubin is a waste product of hemoglobin metabolism. Interruption of the breakdown pathway at any of a number of steps, or a marked increase in load due to red cell destruction, results in an increase in serum bilirubin and (if high enough) clinical jaundice. 

Under normal circumstances senescent red blood cells are taken up and destroyed in the reticuloendothelial system. Through a number of steps the heme molecule of hemoglobin is converted to bilirubin and, tightly bound to albumin, is transported in the plasma to the liver cells. Hepatocytes take up bilirubin, conjugate it to glucuronide and excrete the bilirubin diglucuronide in bile into the duodenum. In the bowel, bacteria break down bilirubin to urobilinogen, 80% of which is excreted in the feces, contributing to the normal stool color. The remaining 20% is reabsorbed and excreted in bile and urine (enterohepatic circulation of urobilinogen). 

Functional or anatomic obstruction at almost any level in this pathway (from hemoglobin breakdown to uptake by the hepatocellular membrane to excretion into the biliary system) will result in jaundice, with an increase in serum bilirubin. A large increase in the breakdown products of hemoglobin alone (e.g., hemolytic anemia) will cause an increase in serum unconjugated bilirubin. If the problem lies after the uptake and conjugation step, the increase is in serum conjugated bilirubin. Causes of jaundice are usually classified as (1) hemolysis, (2) genetic defects in bilirubin handling, (3) hepatocellular disease and (4) obstruction. 

Clinical jaundice is detected when the serum bilirubin level reaches 2-4 mg/ dL (40-80 µmol/L). It is usually preceded by a few days of pale stools (as excretion of bilirubin into the intestine is decreased) and dark urine (due to increased glomerular filtration of conjugated bilirubin). Jaundice is usually first detected in the sclera, although the bilirubin is actually deposited in the overlying conjunctival membranes. Yellow skin without scleral icterus should suggest carotenemia or the ingestion of such drugs as quinacrine. 

Most patients with jaundice, excluding those in whom it is secondary to hemolysis, have nausea, anorexia and discomfort over the liver. There may be hepatomegaly, masses in the epigastrium or pancreas or a dilated gallbladder. Signs of chronic liver disease such as spider nevi or palmar erythema are important. Pruritus may result, presumably from the deposition of bile salts (or a retained pruritogen normally excreted in bile) in the skin. 

Several genetic defects in the conjugation or excretion of bilirubin may cause long-standing unconjugated or conjugated hyperbilirubinemia. 

Initially the most important information is whether the jaundice is due to conjugated or unconjugated hyperbilirubinemia (Figure 3). Serum bilirubin can be fractionated from "total" into conjugated and unconjugated, but the presence of bile in the urine determined by a test strip at the bedside confirms that the bilirubin rise is predominantly in the conjugated form. If the bilirubin is unconjugated, hemolysis or genetic defects are implicated. If the bilirubin is conjugated, "liver biochemical tests" (AST, ALT, GGT and alkaline phosphatase) will help determine if the jaundice is primarily due to obstruction/ cholestasis (high GGT and alkaline phosphatase) or hepatocellular damage (high AST and ALT). Cholestatic jaundice requires ultrasound as the best, first test to detect biliary tract disease. If the jaundice is cholestatic, then an ultrasound of the abdomen is required to determine if there is obstruction of the ducts or intrahepatic bile duct dilatation. 

The management of obstructive jaundice is directed toward the cause where possible (e.g., removal of obstructing gallstone). Jaundice secondary to hepatocellular disease, such as viral hepatitis, does not require any specific treatment. Jaundice due to alcohol, toxin or drug requires withdrawal of the offending agent.