Bilirubinuria is a pathological condition characterized by the presence of bilirubin in the urine. The causes are diseases of the liver and biliary tract . A high concentration of bilirubin turns urine dark brown. The bilirubinuria test together with the urobilinogenuria test (detection of bilirubin derivatives in urine) is used for differential diagnosis of jaundice – parenchymal, hemolytic, obturation. To correct bilirubinuria, therapy of the underlying disease is necessary.
Causes of bilirubinuria
Physiological urobilinogenuria is often observed, since small concentrations of bilirubin metabolites (up to 17 mmol/l) are always found in healthy urine. Bilirubin is also present in the urine of a healthy person (about 7-20 mmol / l), but this amount is not determined by standard methods. Therefore, the detection of bilirubin in the general analysis of urine always indicates some pathology.
In patients taking medications that stain urine red (aminazine, phenazopyridine, medazepam), false bilirubinuria and urobilinogenuria are possible. This is due to the peculiarities of the chemical reactions of urinary test strips. This fact should always be taken into account when interpreting the results of a urine test.
The main cause of bilirubinuria. When the liver parenchyma is affected, bilirubin, both indirect and direct, i.e. bound to glucuronic acid (conjugated), is released into the blood from the destroyed cells. When entering the kidneys with blood flow, bilirubin enters the urine through renal filters, since the glomerular apparatus of the kidneys is able to pass conjugated bilirubin.
The level of bilirubinuria is insignificant at the initial stages of liver damage, then gradually increases in parallel with the severity of the process, reaching maximum figures at the peak stage, after which it begins to decrease under the influence of therapy. Bilirubinuria occurs in the following diseases:
- Viral hepatitis.
- Toxic hepatitis (alcoholic, drug-induced).
- Autoimmune hepatitis (AIH).
- Cirrhosis of the liver.
- Liver damage in severe infections: pneumonia, sepsis, infectious and toxic shock.
- Liver damage in patients with metabolic diseases: hereditary or secondary hemochromatosis, Wilson-Konovalov disease, alpha-antitrypsin-1 deficiency.
- Hepatocellular cancer.
- Parasitic diseases: amoebic liver abscess, echinococcosis.
Diseases of the biliary tract
Very often, bilirubinuria is noted in diseases characterized by a violation of the outflow of bile (obturation, subhepatic jaundice). Due to obstruction of the intrahepatic or extrahepatic biliary tract, hydrostatic pressure increases in their lumen. Conjugated bilirubin begins to diffuse into the blood capillaries, then filtered through the kidneys into the urine.
The degree of bilirubinuria is quite high from the very beginning of the disease, correlates with the severity of the obstruction of the HDL and disappears after its elimination – with surgical treatment almost immediately, with conservative therapy gradually. Diseases of the gastrointestinal tract in which bilirubinuria is observed:
- Calculous cholecystitis, cholelithiasis.
- Purulent cholangitis.
- Primary biliary cirrhosis (PBC).
- Primary sclerosing cholangitis (PSC).
- Cancer of the Fater’s papilla.
A fairly rare cause of bilirubinuria is hereditary disorders of bilirubin metabolism, namely Dabin-Johnson syndrome and Rotor syndrome. These disorders are characterized by a genetic defect in the transport system of organic anions in the bile ducts, which disrupts the flow of conjugated bilirubin into the bile.
Due to the accumulation of excess bilirubin in hepatocytes, part of it enters the blood, then into the urine. Bilirubinuria is insignificant and, since there is no specific treatment for these diseases today, it is observed throughout the patient’s life.
Causes of urobilinogenuria
Urobilinogens are a derivative of bilirubin. Their detection in urine is considered an important diagnostic tool. The presence of urobilinogens in urine can occur with increased destruction of erythrocytes (hemolytic conditions), liver parenchyma lesions, increased reabsorption in the distal colon.
With viral hepatitis, urobilinogenuria reaches its maximum values at the beginning of the disease, then gradually decreases and is practically not determined during the height of the disease and increases again during recovery. Diseases in which urobilinogenuria occurs:
- Diseases accompanied by hemolysis: hemolytic anemia, hemoglobinopathies, conditions after blood transfusions.
- Liver diseases: viral, toxic hepatitis, liver cancer.
- Intestinal diseases: enterocolitis, prolonged constipation, intestinal obstruction.
Causes of urobilinogenuria with bilirubinuria
The simultaneous presence of urobilinogens and bilirubin in the urine is characteristic of parenchymal jaundice, i.e. liver diseases. The detection of these 2 laboratory analytes is an important step in the differential diagnosis of jaundice. The combination of bilirubinuria and urobilinogenuria is observed at the beginning of acute liver disease (for example, in the pre-jaundice stage of acute viral hepatitis) or in the presence of a chronic inflammatory process in the liver tissue (autoimmune hepatitis, chronic viral hepatitis).
If bilirubinuria is detected, you should consult a general practitioner to find out the causes of its appearance. Bilirubinuria is a fairly early sign of damage to the hepatobiliary system, its occurrence often precedes the development of a vivid clinical picture of the disease. At the reception, an examination is carried out, in which attention is paid to the color of the skin and mucous membranes, liver enlargement, symptoms of gallbladder damage (Ker’s symptom, Ortner’s).
Specify the color change of urine and feces. When collecting anamnestic data, they find out which medications the patient is taking. The level of bilirubin, urobilinogens is examined in the clinical analysis of urine using test strips. False negative results are possible with prolonged exposure of the urine sample to light (bilirubin and urobilinogens are oxidized), high concentrations of ascorbic acid in the urine.
Microscopy of urine sediment in some cases reveals crystals of bilirubin. To clarify the etiological factor of bilirubinuria and conduct differential diagnosis, the following examination is prescribed:
- Blood tests. In liver diseases, biochemical blood analysis shows an increase in the concentration of bilirubin, liver enzymes (ALT, AST), in diseases of the gastrointestinal tract – an increase in markers of cholestasis (alkaline phosphatase, gamma-glutamyltranspeptidase), in hemolytic conditions – lactate dehydrogenase, indirect bilirubin. In people with metabolic disorders, indicators of transferrin, ceruloplasmin, metal ions (copper, iron) in the blood are determined.
- Immunological studies. If viral hepatitis is suspected, ELISA and PCR are prescribed to detect specific antibodies (HBsAg, HCV), detection of DNA and RNA viruses. In autoimmune disorders, autoantibodies are studied – antimitochondrial, anticytoplasmic, antibodies to smooth muscle cells.
- Hemolysis tests. To confirm hemolysis, the determination of osmotic resistance of erythrocytes, the Coombs test, electrophoresis of hemoglobin proteins, flow cytometry, etc. are carried out.
- Ultrasound. Ultrasound of the abdominal cavity organs may reveal an increase in the liver, a decrease in its echogenicity, diffuse changes, thickening of the walls of the gallbladder, the presence of concretions.
- Genetic research. In case of suspicion of benign hyperbilirubinemia as the cause of bilirubinuria, genetic tests are prescribed to detect mutations by cytogenetics, polymerase chain reaction.
Methods of self-correction of bilirubinuria, as well as urobilinogenuria, do not exist. Treatment of the underlying disease is necessary. In case of liver diseases, restrictive measures are taken first of all – the appointment of a diet table No. 5 according to Pevsner, the refusal to drink alcohol, the cancellation of the drug (in the case of drug-induced hepatitis). Also , depending on the cause , the following medications are used:
- Antiviral agents. Pelinated interferon, nucleoside analogues (entecavir, ribavirin), reverse transcriptase inhibitors (lamivudine) are used for the treatment of viral hepatitis.
- Choleretic drugs. In diseases accompanied by cholestasis, drugs containing ursodeoxycholic acid are effective.
- Hepatoprotectors. To protect liver cells from excessive damage, ademethionine and glycyrrhizic acid are used.
- Glucocorticoids. Preparations of hormones of the adrenal cortex (prednisone, methylprednisolone) are used to suppress autoimmune inflammation.
- Drugs to combat hemolysis. To prevent hemolysis, immunosuppressants (hydroxyurea), intravenous immunoglobulin are prescribed. To relieve crises, narcotic and non-narcotic analgesics are resorted to.
- Antiparasitic agents. Metronidazole and ornidazole are used for amoebiasis, and mebendazole is used for echinococcosis.
- Chemotherapy. Patients with hepatocellular cancer or cholangiocarcinoma are prescribed multikinase inhibitors (sorafemib, lenvatinib).
Surgical removal of the gallbladder (cholecystectomy) is indicated for patients with calculous cholecystitis and gallstone disease. Currently, endoscopic operations with minimal traumatization are mainly performed. With echinococcosis, a cyst is removed. Splenectomy (removal of the spleen) is the most effective treatment for many diseases accompanied by hemolysis.
After this operation, in order to prevent infectious complications, vaccination against pneumococcus, meningococcus, Hemophilus bacillus is mandatory. In some diseases, such as liver cancer, cholangiocarcinoma, sclerosing cholangitis, the only way to prolong the patient’s life is liver transplantation.
Bilirubinuria, as well as urobilinogenuria, cannot act as a predictor of prognosis. It all depends on the underlying pathology, against which these laboratory abnormalities arose. The most favorable prognosis is for benign hyperbilirubinemia and viral hepatitis A. The most unfavorable outcomes are observed in oncological diseases, cirrhosis of the liver, fulminant course of acute hepatitis. Therefore, if bilirubinuria is detected, it is necessary to contact a specialist.