Definition: what is free, conjugated and total bilirubin?
Bilirubin is a yellow pigment, resulting from the degradation of heme, namely a part of hemoglobin.
Dr Mathieu Kuentz, biologist: This is a natural process of destruction via macrophages, which takes place when the red blood cells are old. The cells are phagocytosed and the heme is degraded and then transformed into bilirubin.
This bilirubin is first free, and binds to plasma proteins – albumin -, transported to the level of the liver, where it is conjugated to become soluble, in order to be eliminated in bile salts through the gallbladder.
Conjugated bilirubin – also called direct bilirubin – then passes through the digestive system where it is degraded. During this transit, part of the bilirubin is reabsorbed and then transported to the liver to be excreted once more in the bile salts. The vast majority of bilirubin is broken down in the intestine into stercobilinogen, brown pigment, and then eliminated in the stools (99%) conferring their brown color. Only a tiny part in the urine (1%)”, says Dr Kuentz
The total bilirubin is the sum of free bilirubin and conjugated bilirubin.
Bilirubinemia: the determination by blood test of bilirubin
The bilirubin test is proposed when an elevation of its level in the blood is suspected. “The bilirubin assay is obtained using a blood sample, blood test, performed in the laboratory. It is rarely carried out in isolation, but mainly associated with a hepatic checkwith the dosage of Gamma GT (GGT), alkaline phosphatase (ALP) and hepatic enzymes (ASAT, ALAT)”, recalls Dr Kuentz.
It is to begin with uniquely total bilirubin level which is measured. If it’s too highwe measure second, free bilirubin. “Then, the conjugated bilirubin is calculated by subtracting the total bilirubin and the free bilirubin”, explains the specialist. Knowing which of the bilirubins – free or conjugated – is increased helps to guide the diagnosis.
Norms: what are the normal values?
The normal concentration of total bilirubin in the blood depends on the person’s age. “The value may vary depending on the assay technique, but in adulthood it is usually less than 20 μmol/litre of blood“, indicates the medical biologist.
Excess: is it serious to have too much bilirubin?
Above 35 μmol/l of bilirubin, there is a cyellow discoloration of tissues (skin and white of the eye) linked to too high a concentration of bilirubin: this is thejaundice.
Excess free bilirubin can lead to brain toxicity. “But these toxic doses are very rarely reached in adults,” reassures Dr. Kuentz. On the other hand, excess bilirubin can be a sign of a potentially serious illness. The danger then does not come from the bilirubin itself, but from the pathology which caused its elevation.
In pediatrics, on the other hand, reaching a threshold of toxic free bilirubin can happen more easily, given the low blood volume of an infant and hepatic immaturity reducing its conjugation and therefore its elimination.
What diseases increase bilirubin?
Dr. Kuentz: There are two main types of etiologies inducing excessive bilirubin, also known as hyperbilirubinemia: either a condition of the hepatic or biliary system which prevents the elimination of bilirubin, or a haemolytic anomaly leading to excessive destruction of blood cells red.
- Hepatobiliary diseases : the most frequent cause is the cholestasis extra or intrahepatic. “Cholestasis prevents the evacuation of bilirubin in the digestive tract, which is therefore pushed back into the blood” describes the medical biologist. This is explained by an increase in conjugated bilirubinand the clinical signs are a discoloration of feces and dark urine.
- Hemolytic origins : they are due to an overdestruction of red blood cells, which exceed the conjugation capacity of the liver. “So this time it’s a accumulation of free bilirubin in the blood”, adds Dr. Kuentz. These haemolytic abnormalities result in a anemia associated with jaundicelinked to excessive destruction of red blood cells.
In the newborn
Newborns may also have excess bilirubin which manifests as infant jaundice. There are two main reasons for this phenomenon:
- a hemolytic abnormality of the newbornwhich may be linked to maternal fetal incompatibility of blood group (ABO or Rhesus),
- a prematurityinducing immaturity of the hepatic systemwhich is not efficient enough to conjugate free bilirubin.
Gilbert’s disease
Gilbert’s disease, or Gilbert’s syndrome, is a pathology benign and quite common — which would affect between 3 and 10% of the population. It is caused by a hereditary deficiency of an enzyme involved in the metabolism of bilirubin.
People with this syndrome have a mildly elevated and fluctuating bilirubinwith inconstant jaundice and slightly yellow conjunctiva. “This pathology does not cause anemia or other symptoms. The liver test is normal,” adds the specialist.
How to lower your bilirubin level?
When the level of bilirubin is too high, it is necessary to understand the cause and to treat it, so that the level returns to normal.
“In case of hemolytic anemia, hemolysis is treated. If it is a biliary cholestasiswe find the cause (lithiasis, fibrosis, tumor, viral hepatitis, liver failure, parasite, etc.) and we treat it”, lists the medical biologist.
Infant jaundice is itself treated with lamps phototherapywhich emit ultraviolet (UV) rays, which modify bilirubin so that it can be more easily excreted.
