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Finding the Source of an Elevated Billirubin

What is Billirubin?. Billirubin is a bi-product of Heme metabolisn250-350mg is produced daily from an adult80% is from the breakdown of HemoglobinThe remaining 25% is from hepatic turnover of molecules such as myoglobin, cytochromes, and catalaseBillirubin in its natural state (unconjugated) is hydrophobic, and insoluble in blood, In order for it to be excreted in the bile, hence eliminated from the body, it must be made more water soluble. .

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Finding the Source of an Elevated Billirubin

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    1. Finding the Source of an Elevated Billirubin Hrach Ike Kasaryan MSIII

    2. What is Billirubin? Billirubin is a bi-product of Heme metabolisn 250-350mg is produced daily from an adult 80% is from the breakdown of Hemoglobin The remaining 25% is from hepatic turnover of molecules such as myoglobin, cytochromes, and catalase Billirubin in its natural state (unconjugated) is hydrophobic, and insoluble in blood, In order for it to be excreted in the bile, hence eliminated from the body, it must be made more water soluble.

    3. What is Billirubin? Uncojugated billirubin is transported bound to albumin in blood, and is delivered to the haptocytes It is than taken up into the hepatocyte by facilitated diffusion Once inside the hapatocyte it is moved to the Endoplasmic Reticulim where the enzyme bilirubin uridine-diphosphate glucuronosyltransferase (billirubin-UGT) is found This enzyme conjugates one molecule of gluco-uronic acid to billirubin, thus making it more water soluble This more soluble form (conjugated billirubin) is than secreted from the hepatocyte into the biliary system via an ATP-dependant transporter.

    4. What are the normal ranges in serum? Total bilirubin – 0.2-1 mg/dl (this does not differentiate conjugated from uncojugated) Indirect bilirubin – 0-0.1 mg/dl (a measure of the unconjugated form) Direct bilirubin – 0-0.2 mg/dl (a measure of the conjugated form)

    5. When do you see Jaundice? Clinical signs of jaundice will start to show up when the total billirubin levels get to around 3 mg/dl. The best place to look for the earliest signs of jaudice is under the tongue.

    6. So you have an elevated Total Billirubin, NOW WHAT?

    7. Approach to elevated Billirubin Any disease process that interferes with the production, transport, uptake, conjugation, secretion and elimination of billirubin can cause the levels to rise The differential diagnosis of causes of an elevated billirubin is exhaustive and it is important to have a systematic approach to narrow the differential as specific as possible So what is the first step?

    9. Elevated Indirect Billirubin The differential for elevated indirect-billirubin is still very exhausting You can have an elevated indirect for: Increased production of Billirubin Decreased Uptake into the Hepatocyte Decreased Conjugation in the hepatocyte

    17. Elevated Direct Billirubin Now what if the Direct Billirubin is elevated? Some clues to the presents of an elevated Direct Billirubin PURITIS Billirubin present in the urine (b/c it is water soluble) The differential now narrows a lot more with an elevated direct Billirubin, which would be due to anything disrupting transport out of the hepatocyte and out of the billiary system

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