Jaundice, Canine - contd.
Jaundice is a yellowish discoloration of the skin, sclera -- the whites of the eyes -- and mucous membranes of the mouth. It occurs when the amount of bilirubin produced in the body exceeds the liver's -- and to a lesser extent, the kidneys' -- ability to excrete it. An elevated serum bilirubin level will also result in bilirubin deposition in many other tissues of the body. However, jaundice is not apparent in darker tissues and internal organs. Jaundice becomes noticeable when serum bilirubin reaches 2 mg/dl.
Bilirubin is an end product of heme metabolism. Heme is the iron-containing component of hemoglobin, which is the molecule in red blood cells responsible for carrying oxygen to the body's tissues. Heme is also a component of myoglobin, which resembles hemoglobin, and is present in muscle protein for oxygen transport. When red blood cells break down, or hemolyze, heme is separated from the other part of the hemoglobin molecule and is metabolized to bilirubin. A small amount of bilirubin in the blood is a normal consequence of the destruction of old red blood cells. The normal wear and tear of muscle protein also contributes to this normal level of serum bilirubin, although not as much as red blood cell hemolysis produces.
Any disease process that produces excess bilirubin or interferes with its metabolism and excretion from the body produces the characteristic signs of jaundice. In dogs, there are three basic classes of disease processes that cause jaundice: pre-hepatic, hepatic, and post-hepatic. Pre-hepatic jaundice is due to excessive red blood cell breakdown, or hemolysis, which results in anemia and an abnormal increase in serum bilirubin. Pre-hepatic jaundice may also occur when significant muscle damage occurs. When muscles are significantly injured, heme is released from myoglobin and is metabolized to bilirubin.
Hepatic jaundice is due to a disease or disorder located within the liver. Such intra-hepatic disease may be primary or secondary. Primary liver diseases originate in the liver; secondary ones develop elsewhere in the body and then spread to the liver or by other means cause disease within it. If a jaundiced dog is not anemic and if there is no evidence of bile duct obstruction or gallbladder disease on x-ray and ultrasound studies, then intra- hepatic disease is likely.
A number of mechanisms underlie the development of hyperbilirubinemia associated with liver disease, both primary and secondary. Necrosis, or death, of liver cells will impair the liver's functional capacity to store and metabolize bilirubin. The formation of scar tissue in the liver in response to injurious agents can cause obstruction of bile flow within the liver, thus preventing its excretion. Compression of the intrahepatic duct system by tumors can block the flow of bilirubin-containing bile flow also. Inflammatory conditions of the liver can cause intrahepatic congestion that can block the flow of bile through the liver as well.
Post-hepatic jaundice occurs with bile duct obstruction or biliary tract leakage. Normally bile is eliminated in the gastrointestinal tract. When this normal elimination of bilirubin is impaired, serum concentrations of bilirubin will rise. Obstruction to bile flow outside the liver will cause secondary bile flow obstruction in the liver. When post-hepatic bile flow is obstructed, leakage of bile from the obstructed biliary tract into the abdominal cavity can readily occur. The bile, including bilirubin, will be absorbed through the abdominal cavity wall and enter the blood stream.
A persistently high level of serum bilirubin, as evidenced by jaundice, can have secondary toxic effects on various tissues, including the kidney and liver. A pre-hepatic or post-hepatic disease process associated with hyperbilirubinemia could result in secondary hepatic toxicosis that could further impair the affected dog's ability to process bilirubin.
