Bilirubin (total, conjugated, unconjugated) and Jaundice



Bilirubin, a yellow compound that occurs in the body’s normal waste material processing, plays a pivotal role in the breakdown process of red blood cells. It’s not only a substance of clinical interest but also a key indicator of various health conditions. This article delves into the intricacies of bilirubin, covering its types, normal ranges, causes of elevation, and associated symptoms, focusing mainly on jaundice.

What is bilirubin?

Bilirubin is produced during the body’s process of breaking down red blood cells. The liver plays a crucial role in converting bilirubin into a form that can be excreted through bile and urine. Understanding its types is essential for diagnosing and monitoring liver health and function.

  • Total Bilirubin: This measures the total amount of bilirubin in the blood, including both conjugated and unconjugated forms.
  • Conjugated (Direct) Bilirubin: This form of bilirubin is water-soluble and has been processed by the liver, ready to be excreted in bile.
  • Unconjugated (Indirect) Bilirubin: This is the form before it reaches the liver, insoluble in water, and bound to albumin in the bloodstream.

Normal range

The normal range of total bilirubin typically lies between 0.3 and 1.2 milligrams per deciliter (mg/dL), though these values can slightly vary depending on the laboratory and measurement methods used. For adults, direct (conjugated) bilirubin levels are usually under 0.3 mg/dL.

Causes of elevated bilirubin

Elevated bilirubin levels can be a marker for several conditions, often related to the liver, bile ducts, or red blood cells. Some common causes include:

  • Hemolytic Anemia: Increased breakdown of red blood cells leads to higher levels of unconjugated bilirubin.
  • Liver Diseases: Conditions such as hepatitis, cirrhosis, and liver cancer can impair the liver’s ability to process and excrete bilirubin, resulting in elevated levels.
  • Bile Duct Obstruction: Gallstones, inflammation, or tumors that block the bile ducts can prevent bilirubin from being excreted, leading to increased levels of conjugated bilirubin.
  • Gilbert’s Syndrome: A genetic condition that impairs the enzyme responsible for converting unconjugated bilirubin into its conjugated form.

Symptoms of elevated bilirubin

Elevated bilirubin levels can lead to jaundice, a condition characterized by yellowing of the skin and eyes. Other symptoms may include:

  • Dark urine, due to the excretion of excess bilirubin through the kidneys.
  • Pale stools, if bile duct obstruction prevents bilirubin from reaching the intestines.
  • Itching, resulting from bilirubin accumulating in the skin.
  • Fatigue, abdominal pain, and weight loss, which may indicate underlying liver disease or bile duct obstruction.

Types of jaundice

Jaundice, characterized by the yellowing of the skin and eyes, occurs when there’s an accumulation of bilirubin in the body. Bilirubin is a byproduct of the normal breakdown of red blood cells, processed in the liver, and excreted through bile. Jaundice is not a disease but a sign of an underlying condition affecting bilirubin metabolism or elimination. It can be categorized based on where the problem in the bilirubin processing pathway occurs: pre-hepatic, intra-hepatic, and post-hepatic (extra-hepatic).

Pre-hepatic jaundice

Pre-hepatic jaundice, also known as hemolytic jaundice, occurs before bilirubin is processed by the liver. It results from the rapid breakdown of red blood cells, leading to an increase in the production of unconjugated bilirubin, which the liver cannot process fast enough. This type of jaundice is characterized by elevated levels of unconjugated bilirubin in the blood. Causes can include:

  • Hemolytic anemias, where red blood cells are destroyed faster than they can be made, due to conditions like sickle cell anemia, thalassemia, or autoimmune diseases
  • Certain medications or toxins that lead to increased red blood cell destruction
  • Genetic conditions, such as Gilbert’s syndrome. Gilbert’s syndrome is a common, mild liver disorder in which the liver doesn’t properly process bilirubin, a byproduct of the breakdown of red blood cells. People with Gilbert’s syndrome have an inherited deficiency in an enzyme needed to convert unconjugated bilirubin into its conjugated form, which can be excreted from the body. As a result, bilirubin can build up in the blood, leading to mild jaundice, particularly during periods of illness, fasting, or stress. Gilbert’s syndrome is usually harmless and often doesn’t require treatment. Most people with this condition lead normal, healthy lives without any complications, and it’s often discovered incidentally during blood tests for other conditions.

Intra-hepatic jaundice

Intra-hepatic jaundice occurs within the liver due to impaired bilirubin processing, often because of liver cell damage or dysfunction. This type can involve either conjugated or unconjugated bilirubin, depending on the specific liver dysfunction. Causes include:

  • Hepatitis (viral, alcoholic, autoimmune)
  • Cirrhosis, where normal liver tissue is replaced by scar tissue, hindering the liver’s ability to function.
  • Drug-induced liver injury
  • Genetic disorders, such as Dubin-Johnson syndrome or Rotor syndrome, that specifically impair the liver’s ability to conjugate and secrete bilirubin

Post-hepatic (extra-hepatic) jaundice

Post-hepatic or extra-hepatic jaundice, also known as obstructive jaundice, occurs when there’s a blockage in the bile ducts that prevents conjugated bilirubin from being excreted into the intestine. This type of jaundice is characterized by elevated levels of conjugated bilirubin, which may leak into the urine, causing it to become dark. Causes include:

  • Gallstones blocking the bile ducts
  • Tumors that press on the bile ducts
  • Pancreatic cancer
  • Strictures (narrowing) of the bile ducts, which could be due to surgery, inflammation, or chronic pancreatitis
  • Parasitic infections

When is high bilirubin an issue of concern?

Elevated bilirubin levels can be concerning and warrant medical attention in several contexts. While mild elevation might not always signify a severe condition, particularly in benign disorders like Gilbert’s syndrome, there are scenarios where high bilirubin levels indicate underlying health issues requiring prompt evaluation and treatment. Here are situations when elevated bilirubin becomes a concerning issue:


In newborns, elevated bilirubin levels often lead to jaundice within the first week of life. While common and sometimes benign, extremely high levels of bilirubin in infants can lead to a condition known as kernicterus, a form of brain damage. Therefore, newborn jaundice must be monitored and treated appropriately to prevent serious complications.

Sudden or severe increase

A sudden or significant increase in bilirubin levels, especially if accompanied by symptoms such as jaundice (yellowing of the skin and eyes), dark urine, light-colored stools, and itching, can indicate acute liver dysfunction or obstruction of the bile duct. Conditions such as acute hepatitis, gallstones, or a tumor blocking the bile duct could be the cause.

Chronic liver conditions

People with chronic liver diseases, including hepatitis, cirrhosis, and liver cancer, may experience fluctuations in bilirubin levels. Persistent or worsening elevation could indicate liver function deterioration, requiring medical intervention to manage the underlying condition and prevent further liver damage.

Hemolytic anemias

When elevated bilirubin is due to increased breakdown of red blood cells, as seen in hemolytic anemias, it can be concerning. This excessive destruction can lead to anemia, requiring treatment to address the underlying cause and prevent complications like fatigue, weakness, and severe anemia.

Signs of systemic involvement

Elevated bilirubin levels that are part of systemic symptoms, including fever, fatigue, abdominal pain, and weight loss, may indicate a more severe or systemic condition like infections, autoimmune diseases, or malignancies affecting the liver.

Ineffective treatment

For individuals already diagnosed with conditions known to elevate bilirubin levels, ineffective treatment or management of their condition can be concerning. It may suggest the need for a reevaluation of their treatment plan or further investigation into other potential causes of elevated bilirubin.


Bilirubin is a critical component in the body’s processing of waste materials, particularly in the breakdown and elimination of red blood cells. Understanding the types of bilirubin, their normal ranges, and what causes levels to elevate provides essential insights into liver health and overall bodily function. Elevated bilirubin levels can indicate several conditions that require medical evaluation and intervention, highlighting the importance of regular health screenings and liver function tests.

Identifying the type of jaundice is crucial in diagnosing the underlying cause, as it narrows down the possible conditions and guides further testing and treatment. For example, treatment might involve managing liver disease, removing a blockage in the bile duct, or treating infections or genetic conditions. The presence of jaundice, regardless of the type, is a sign that medical evaluation is needed to determine its cause and appropriate treatment.

Last update: 13 April 2024, 10:56


Gastroenterologist - Hepatologist, Thessaloniki

PhD at Medical School, Aristotle University of Thessaloniki, Greece

PGDip at Universitair Medisch Centrum Utrecht, The Netherlands

Ex President, Hellenic H. pylori & Microbiota Study Group