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Urobilinogen in urine

WHAT IS UROBILINOGEN? ORIGINS AND METABOLISM OF UROBILINOGEN

UROBILINOGEN is one of end-products of BILIRUBIN.

Small quantities of bilirubin is being produced in a body constantly. It is a physiological process. The main source of bilirubin in the body is hemoglobin of red blood cells (RBCs).

main article

Indirect and direct bilirubin: origins, properties and metabolism

Having knowledge of bilirubin metabolism allows us a better understanding of some reasons for its elevated level. Contrary to popular belief, it is by no means always a sign of liver disease

Origins and metabolism of urobilinogen
Origins and metabolism of urobilinogen

There are two key points in urobilinogen metabolism: the liver and the intestine. All the amount of bilirubin is excreted by the liver into the intestine with bile. In the intestine resident microorganisms transform bilirubin into urobilinogen. Then urobilinogen parts ways: one half is excreted away and another one is being reabsorbed from the intestine into bloodstream and handled by the liver. There it happens once again: urobilinogen turns into bilirubin and is excreted into the intestine with bile. Only insignificant amounts of urobilinogen (<1%) is excreted by kidneys in urine.

Thus a certain percentage of urobilinogen/bilirubin constantly circulates between liver and intestine alternately becoming either one form or another.

Urobilinogen is a colourless substance. It turns into brown substance UROBILIN if it has an opportunity to join with an oxygen of the air. Because of that the urine that contains urobilinogen, gets darker with time. And vice versa, the urine that contains bilirubin is initially dark.

CAUSES OF UROBILINOGEN APPEARANCE IN URINE

A. HEMOLYTIC ANEMIA

A mechanism called HEMOLYSIS (massive breakdown of RBCs) underlies this group of diseases. A lot of things can cause hemolysis, but the result is always the same: massive destruction of RBCs leads to production of excess bilirubin. Accordingly, the amount of urobilinogen rises too. The liver is overwhelmed. That's why some part of urobilinogen is on its own and is eliminated from the body with urine.

Of course, one direct consequence of hemolysis is anemia. Its symptoms may vary from very slight to serious with severity of hemolysis. The evidence of anemia are skin paleness and dizziness. Blood test shows a decreasing amount of RBCs and low level of hemoglobin. Also there is high percentage of so called reticulocytes. These are young unripe RBCs that are not able yet to perform their functions properly. Trying to make up for RBC deficiency, the body sends these reticulocytes to bloodstream without waiting for them to mature.

Main causes of hemolytic anemia:

  • Hereditary hemolytic anemia
  • Autoimmune hemolytic anemia
  • Infectious diseases
  • Hemolytic disease of the newborn (HDN), or erythroblastosis fetalis
  • Drug-induced hemolytic anemia
  • Exposure to hemolytic poisons
Distinctive features of hemolytic anemia:
  • elevated indirect bilirubin in blood, direct bilirubin is within normal range
  • no bilirubin in urine
  • spleen enlargement (splenomegaly)

in more detail: Causes of hemolytic anemia

B. LIVER CONDITIONS

Most of liver conditions more or less disrupt the mechanism of bilirubin and its derivatives. Hepatic cells partially or totally lose the ability to catch urobilinogen that is reabsorbed in the intestine.

Main causes of these liver conditions:

  1. Acute and chronic hepatitis:
    • viral hepatitis
    • parasitis hepatitis
    • bacterial hepatitis
    • alcoholic hepatitis
    • drug-induced hepatitis
    • toxic hepatitis
    • autoimmune hepatitis
    • hepatitis induced by inherited disorders of metabolism
  2. Cirrhosis
  3. Tumors of liver
  4. Some hereditary diseases
Distinctive features of these conditions:
  • high direct bilirubin in blood
  • bilirubin in urine
  • high level of transaminases (ALT, AST)

in more detail: Causes of high bilirubin: liver conditions

NORMAL LEVEL OF UROBILINOGEN IN URINE

Normal level of urobilinogen 0.1 - 1.0 EU/dL

FALSE POSITIVE UROBILINOGEN TEST

Some meds can be the cause of false positive urobilinogen test, because they react with Ehrlich's reagent all like urobilinogen:

  • para-aminosalicylic acid
  • antipyrine
  • chlorpromazine
  • phenazopyridine
  • phenothiazine
  • sulfadiazine
  • sulfonamide

To avoid the mistakes when interpreting the urine test, other factors and symptoms should be taken into consideration.

TWO-PHASE UROBILINOGEN APPEARANCE IN URINE IN ACUTE HEPATITIS

Two-phase urobilinogen appearance in urine in acute hepatitis
Two-phase urobilinogen appearance in urine in acute hepatitis

The acute hepatitis is often accomponied with a strange phenomenon that is two-phase appearance of urobilinogen in the urine.

Initially things are happening the way they are supposed to do: along with a high level of bilirubin in blood and jaundice, there are both bilirubin and urobilinogen in the urine. But within days urobilinogen disappears and this is not good news at all. What happened is that described in a previous section: a diseased liver doesn't produce the bile anymore and/or the bile flow in the bile ducts stopped (so-caled cholestasis). As we already know, urobilinogen is produced from bilirubin in the intestine. In this case there is nothing to make it from.

After a while urobilinogen is back. Now it's a good thing. The liver is getting better and the bile managed to enter the intestine. But the liver is still not able to effectively dispose of urobilinogen that returns to it from the intestine. So urobilinogen is on its own and is excreted with urine.

SUMMARY A: INTERPRETING THE RESULTS OF UROBILINOGEN TEST

Uro­bilinogen in urine Bilirubin in urine Inter­preting the results
yes no hemolytic anemia
yes yes liver conditions
no yes obstructive jaundice
This simple interpretation algorithm doesn't deal with the possibility of false positive urobilinogen test. That's why a wide range of tests and symptoms given in the table below should be taken into account.

SUMMARY B: HOW TO FIND OUT THE CAUSES OF VARIATIONS IN UROBILINOGEN LEVEL IN URINE

Hemo­lytic anemia Hepa­titis, cirrhosis Obstruc­tive jaundice
Urobilinogen in urine yes yes no
Bilirubin in urine no yes yes
Indirect bilirubin high normal or high normal
Direct bilirubin normal or slightly high high high
Hemoglobin low normal normal
Reticulocytes (unripe RBCs) in blood high normal normal
Transaminase (ALT, AST) normal high normal
Alkaline phosphatase (due to liver isoenzyme) normal or low normal or slighly high high
Signs of anemia (paleness, dizziness etc) yes no no
Splenomegaly (enlargement of spleen) yes no no
Feces discoloration no possible yes