Pathophysiology

Jaundice (also called icterus) is the yellowish discoloration of the sclera, skin, and mucous membranes caused by the deposition of bile pigments associated with elevated levels of bilirubin in the blood (hyperbilirubinemia). Jaundice can usually be clinically detected when serum bilirubin levels reach 2.0 to 2.5 mg/dL or above, about twice the upper level of normal. It is usually first noticed in the sclera because scleral tissue contains a large amount of elastin, which has a high affinity for bilirubin. Jaundice is easier to detect in people with light complexions and in the presence of significant anemia. The brownish discoloration of the sclerae in many people with darker complexions may be confused with scleral icterus and makes it more difficult to detect. A greenish tint to the skin indicates long-standing jaundice during which some of the bilirubin deposited in the skin has been metabolized to biliverdin. A yellow-orange discoloration of the skin can be caused by the presence of high levels of carotene in the blood (resulting from the dietary intake of large amounts of beta-carotene) or by longstanding hemochromatosis. Neither of these will discolor the sclera, however.

Bilirubin, a breakdown product of hemoglobin from injured or senescent red blood cells and other heme-containing proteins, is produced in the reticuloendothelial system and then released into the plasma, where it is bound to albumin. Hepatocytes take up the bilirubin, conjugate it (mostly as the mono- and diglucuronide) and excrete it through the bile channels into the small intestine. In the gut, bacterial enzymes release some of the bilirubin and reduce it to urobilinogen and the other pigments that give fecal material its typical color. Some urobilinogen is reabsorbed into the portal circulation, where most is taken up by the liver and reexcreted into the bile. A small amount reaches the kidneys and is excreted unchanged into the urine. Hyperbilirubinemia and jaundice, therefore, can be produced by an overproduction of bilirubin in the reticuloendothelial system, a failure of hepatocyte uptake of bilirubin, a failure of the hepatocyte to conjugate or excrete bilirubin, or an obstruction of biliary excretion into the intestine (I,a.b!e..,8.0,-,.1..)1

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