Urine Bilirubin, Bilirubinuria
Urine Bilirubin
Sample for urine bilirubin
- The sample is urine.
- A random sample can be taken.
Precautions for urine bilirubin
- A fresh urine sample is needed.
- Store at 2 to 8 °C for no longer than 24 hours.
- Even at room temperature, it converts into biliverdin.
- Avoid urine to light. Avoid daylight or fluorescent light.
- Light converts bilirubin to biliverdin, which is not detected by routine methodology.
- Exposure to light urine will decrease bilirubin.
The false-positive:
- A false positive result is seen in the metabolites of drugs like phenazopyridine.
- The substances which color the urine red or turn red in the acid medium like:
- Chlorpromazine.
- Phenothiazine.
- Indol.
- Pyridium
- The substances which color the urine red or turn red in the acid medium like:
False-negative:
- False-negative results are seen:
- With the ascorbic acid intake.
- Oxidation of bilirubin to biliverdin.
- Increased nitrite concentration.
- Hydrolyzation of bilirubin diglucuronide to free bilirubin.
Indications for urine bilirubin
- Diagnose hepatitis.
- Diagnose any liver damage.
- Monitor the treatment of hepatitis.
Definition of urine bilirubin
- It is the conjugated bilirubin that is excreted from the kidneys and appears in the urine.
- Unconjugated bilirubin can not pass the glomerular filtration, so it is not present in the urine.
Pathophysiology of bilirubin metabolism
- A detectable amount of bilirubin is not found in the urine.
- The breakdown of hemoglobin leads to bilirubin formation, which goes to the liver.
- From the liver excreted into the bile.
- Excretion of bilirubin is seen in obstructive jaundice and not in hemolytic jaundice unless there is liver damage.
- Following the diagram explains bilirubin metabolism and its excretion.
Clinical significance of urine bilirubin:
- Urine bilirubin is the early sign of:
- Hepatocellular disease.
- Intra or extrahepatic biliary obstruction.
- Bilirubin appears in the urine before other signs of hepatitis appear.
- Bilirubin’s presence or absence in the urine is helpful for clinical jaundice.
- Bilirubin is the major component of bile.
- If there is an obstruction to the bile, that will lead to conjugated hyperbilirubinemia.
- Conjugated bilirubin is water-soluble, so that it will appear in the urine.
- The presence of bilirubin in urine indicates defects after conjugation and defects in excretion.
- Bilirubin is a yellowish pigment in the bile which is produced by the liver.
- Bilirubin in urine color = dark yellow or orange.
- This test measures the amount of bilirubin excreted in the urine.
- The presence of bilirubin in the urine indicates jaundice.
Normal urine bilirubin
- Normally bilirubin is absent in the urine (0 to 0.02 mg/dL or 0 to 0.34 µmol/L).
- Even traces indicate liver disease like hepatitis.
Procedure for urine bilirubin:
The following tests are used to check bilirubin in the urine:
- Fouchet’s test.
- Strip method.
- Tablet method.
Tablet method
- In this test, bilirubin form stable diazonium salt that produces blue-purple azobilirubin.
- This reaction is specific to bilirubin.
- Read the result after 60 seconds.
- Moisture will deteriorate the reagents.
- Always use a white dry tablet.
- It detects the urine bilirubin level as low as 0.5 mg/dL.
Strip method:
- These are mostly available as multiple test strips.
- This reaction depends upon the diazo reaction. These strips are impregnated with the diazo reagent.
- This method detects a concentration of 0.5 mg/dL or greater.
- Insert the strip in the urine no longer than one second.
- After 60 seconds, the Diazo reagent reacts with bilirubin at an acidic pH.
- A pink to red-violet color is produced.
- The intensity of the color depends upon the concentration of the bilirubin in the urine.
Fouchet’s or Ferric chloride reaction:
- Add urine to barium chloride, and it will form a barium sulfate precipitate containing bilirubin.
- Barium sulfate + bilirubin filter and get the precipitate.
- Add ferric chloride (Fouchet’s solution) to the above precipitate.
- Bilirubin oxidized to biliverdin, which gives green-blue color.
Comparison of Fouchet’s reaction and Diazo’s reaction:
Characteristics | Fouchet’s reaction (FeCl3) | Diazo reaction |
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The various strips detection level:
Type of the strip | The detection level of bilirubin |
Ictotest | 0.05 to 0.1 mg/dL |
Multistix | 0.4 to 0.8 mg/dL |
Chemstrip | 0.5 mg/dL |
Increased urine bilirubin is seen in:
- Hepatitis and liver diseases are caused by infection or exposure to toxic agents ( cirrhosis ).
- Obstructive biliary tract disease.
- Liver or biliary tract tumor.
- Septicemia.
- Hyperthyroidism.
- Gallstones.
- Metastatic tumor in the liver.
- Drugs
- Dubin-Johnson syndrome.
- Rotor syndrome.
Urine Bilirubin/urobilinogen differential diagnosis
Test | Normal | Conjugated (Direct) hyperbilirubinemia | Unconjugated (Indirect) hyperbilirubinemia | Conjugated (Direct) hyperbilirubinemia |
Etiology | Biliary obstruction | Hemolysis | Hepatitis (liver injury) | |
Urine bilirubin | negative | positive (Increased) | Usually absent | positive |
Urine urobilinogen | positive/negative | Absent | Positive (Increased) | positive (+++) |
- Urine bilirubin is negative in hemolytic disease.
Bilirubin (urine and blood) in various types of jaundice:
Type of the jaundice | Etiology | Urine bilirubin | Urine urobilinogen | Blood bilirubin | Fecal appearance |
Hemolytic or prehepatic |
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Negative (Usually absent) | Increased | Raised | Dark brown |
Hepatic or hepatocellular |
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Increased (variable) (+ or -) |
Increased (++) |
An increased, variable amount | Normal or pale |
Post-hepatic or obstructive |
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Increased (+++) | Absent (or very low) |
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Clay-colored, acholic |
Questions and answers:
Question 1: Can unconjugated bilirubin pass through the kidneys?
Question 2: When urine bilirubin appears in the urine in jaundice?
I think there is a mistake in the table comparing bilirubin and urobilinogen in the urine.
in obstructive jaundice, the urobilinogen should be absent/reduced, not increased. Whereas in hemolytic anemia, the urobilinogen is increased, not negative
Table corrected, thanks for the comment.