Dr Anuja Mahajan explains the importance of checking serum bilirubin levels
Bilirubin explained
The word jaundice or icterus in medical terminology which manifests clinically as yellow-orange discolouration of the sclera or white of the eyes and skin always draws a reactionary question “what’s the serum bilirubin level?” Serum bilirubin is one of the components of the prescribed liver function test (LFT) where the functional capacity of the liver cells appears impaired and by itself is not of much diagnostic help except for the fact that it helps confirm the presence of jaundice.
To better understand this complicated biochemical laboratory parameter, we need to understand the process of its formation in the body. Bilirubin is the breakdown product of senescent and or fragile red blood cells (RBCs) whose normal life span is 120 days. The haemoglobin from the red cells releases haeme from which the iron is removed to be reutilised in the body and the remaining product is converted into bilirubin. This breakdown normally occurs in the spleen which is referred to as the graveyard of the red cells and in the bone marrow.
Forms of bilirubin
Essentially there are two distinct forms of bilirubin present in the body and when their levels are raised, they point towards the possible causative pathology. In the laboratory, total bilirubin and direct bilirubin (that which is bound to albumin) are estimated and their difference gives the amount of indirect bilirubin (that which is not bound to albumin). The normal reference ranges of these components are:
- Total bilirubin – 0-1 mg/dL
- Direct bilirubin – 0-0.3 mg/dL
- Indirect bilirubin – 0.1-1.0 mg/dL The indirect bilirubin is the first to be
formed, whose production when exceeds the rate at which liver cells can handle the load results in increased total and indirect bilirubin levels. This is seen in the new-born as a physiological condition called neonatal jaundice which is due to the development of large caput or swelling in the scalp during prolonged labour. Neonatal jaundice, if not treated aggressively with phototherapy and drugs, results in bilirubin getting deposited in the basal ganglion of the brain, a condition called kernicterus, leading to lasting signs and symptoms of nervous system dysfunction later in life. This is classically seen when indirect bilirubin levels go beyond 18 mg/dL. Other conditions where we encounter raised indirect bilirubin are Gilbert’s and Crigler- Najjar’s Disease where due to a genetic defect, the binding of bilirubin with albumin is impaired. This is also seen in conditions with increased breakdown of circulating RBCs or haemolysis as seen in hereditary spherocytosis.
The direct bilirubin gets bound (conjugated) with albumin in the liver depending upon the functional efficiency of the hepatocytes which normally have a functional reserve of 5-10 times when required. This, in turn, gets secreted into the biliary fluid and excreted in the small intestine where it gets deconjugated from the attached albumin.
This bilirubin may exit the body through stools as stercobilinogen and through urine as urobilinogen. However, the majority (95 per cent) is reabsorbed and goes back to the liver to once again get conjugated and secreted as bile.
What causes high bilirubin levels?
There is a myriad of conditions where we encounter an increase in direct bilirubin levels which once again manifest clinically only as jaundice. The blood levels of direct bilirubin usually do not correlate with the extent of jaundice being more in the rising phase and less in the receding phase.
Functional defects of the hepatocytes or a mechanical obstruction to the outflow of bile results in increased levels of direct bilirubin as seen in viral hepatitis, necrosis of hepatocytes, Dubin-Johnson syndrome
where there is a functional impairment of conjugation, impacted gall stones, liver cirrhosis, tumours of the gall bladder and bile duct and in periampullary carcinoma of the pancreas where there is a mechanical obstruction to the excretion of bile.
Limitations
However, in tumours of the liver like hepatocellular carcinoma, the serum bilirubin levels deceptively remain normal leading to this tumour often being missed until they acquire a very large size and become inoperable. So we can see that though the determination of serum bilirubin levels is helpful, at the same time they by themselves are not diagnostic of any specific pathology except viral hepatitis and hence should be interpreted with due caution.
Dr Anuja Mahajan is a Consulting Pathologist.
