Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and whites of the eyes due to high bilirubin levels.
The majority of daily production of bilirubin is derived from breakdown of senescent red cells by the mononuclear phagocytic system, especially in the spleen, liver, and bone marrow.
First the macrophage eats up the blood cell, and hemoglobin is broken up into heme and globin, the globin is further broken into amino acids.The heme on the other hand is split into iron and protoporphyrin, protoporphyrin is then converted into unconjugated bilirubin. Unconjugated bilirubin is the form of bilirubin that’s lipid-soluble, meaning it’s not water- soluble.
Bilirubin in the bloodstream is usually in a free, or unconjugated, state; it is attached to albumin as it is transported. Once in the liver it conjugates with glucuronic acid by an enzyme called uridine glucuronyl transferase, making it now water soluble and sent to the gallbladder for storage as bile.
Jaundice, where the sclerae and skin turn yellow, occurs due to an increase in either conjugated or unconjugated bilirubin in the circulation. For unconjugated bilirubin to increase, there must be either increased production of bilirubin, decreased up take of bilirubin by the liver, or decreased con jugation of bilirubin by the liver. Since bilirubin comes from the breakdown of old or damaged red cells, any cause of hemolytic anemia would lead to increased production of bilirubin. This increase can exceed the liver's capacity to conjugate, leading to an elevation of unconjugated bilirubin. Congestive heart failure reduces blood flow to the liver, which can decrease delivery of bilirubin for conjugation, resulting in unconjugated jaundice. Decreased uptake and conjugation can also occur secondary to two genetic
syndromes : Crigler-Najjar and Gilbert's. Crigler Najjar
syndrome is where there’s pretty much no uridine glucuronyl transferase and therefore no ability to conjugate unconjugated bilirubin, this will lead to high levels of unconjugated bilirubin, and likely unconjugated bilirubin deposits in the brain and Crigler Najjar syndrome is usually fatal. Gilbert’s syndrome is where their uridine glucuronyl transferase enzyme activity is low and has a hard time cranking up when needed. Unfortunately, if something comes along that increases hemolysis, like infection, stress, or starvation, the unconjugated bilirubin load will increase which can easily overwhelm these hepatocytes, cause buildup of unconjugated bilirubin in the blood and lead to jaundice.
What about increases in conjugated bilirubin? If the elevation of bilirubin is largely conjugated, this means that the bilirubin has made it into the liver and conjugation has occurred. What would cause a backup of conjugated bilirubin in the blood? Either the liver does not accomplish the final step of secreting the bilirubin into the bile ducts, or the biliary tree is obstructed.These blockages could be anything
from gallstones, pancreatic carcinomas and cholangiocarcinomas, to parasites like the liver fluke.
Dubin-Johnson syndrome is an autosomal recessive disorder where there’s a deficiency in the protein that helps move conjugated bilirubin from the liver cell to the bile
ducts ,called MRP2, so conjugated bilirubin builds up in the hepatocyte.
It’s thought that when the MRP2 transporter is defected, another transporter, MRP3 is upregulated, though this transporter moves it into the interstitial space and blood flow, as opposed to the bile canaliculus, so in this case you’ll have increased conjugated bilirubin in the blood.
Jaundice is not the only color change when there is elevated bilirubin in the circulation due to obstruction. Excess pigment that arrives in the urine leads to dark urine. Lack of
bile pigment making it to the GI tract leads to lack ofthis pigment in the stool. Bile salt deposits in the skin lead to severe itching.
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