Bilirubin is a yellowish substance produced naturally in the body as a waste product when old red blood cells break down. It is the pigment that gives bile its distinctive yellow color, and it also contributes to the brown color of stool. While typically expelled from the body through the intestines, bilirubin may also act as an antioxidant, potentially offering protection against cardiovascular disease.
Understanding Bilirubin
Bilirubin’s journey begins with the breakdown of hemoglobin from red blood cells, which occurs in specialized cells called macrophages. This process first yields biliverdin, a green pigment, which is then converted into unconjugated, or indirect, bilirubin. Unconjugated bilirubin is not water-soluble, so it binds to a protein called albumin for transport to the liver.
Once unconjugated bilirubin reaches the liver, liver cells modify it by attaching glucuronic acid. This process, called conjugation, makes the bilirubin water-soluble, transforming it into conjugated, or direct, bilirubin. Conjugated bilirubin then mixes with bile and is excreted through the intestines. The distinction between unconjugated and conjugated bilirubin is important because it helps medical professionals identify where in the bilirubin processing pathway a problem might be occurring.
Common Causes of Elevated Bilirubin
Elevated bilirubin levels, or hyperbilirubinemia, can arise from issues at different stages of its processing and excretion. Causes are broadly categorized as pre-hepatic (before the liver), hepatic (within the liver), or post-hepatic (after the liver). Each category points to different underlying health conditions.
Pre-hepatic causes involve conditions that lead to an increased breakdown of red blood cells, overwhelming the liver’s capacity to process the bilirubin produced. This accelerated red blood cell destruction is often seen in hemolytic anemia. Genetic conditions like sickle cell anemia or thalassemia, autoimmune disorders, and even reactions to blood transfusions can trigger such excessive breakdown. Additionally, ineffective erythropoiesis, where immature red blood cells are prematurely destroyed, also contributes to pre-hepatic hyperbilirubinemia.
Hepatic causes involve problems directly within the liver that impair its ability to process bilirubin. This can result from liver diseases such as hepatitis. Chronic conditions like cirrhosis also hinder bilirubin processing. Certain medications, excessive alcohol consumption, and genetic conditions like Gilbert’s syndrome, which causes a mild reduction in the enzyme needed for bilirubin conjugation, can also lead to elevated bilirubin levels within the liver.
Post-hepatic causes occur when there is an obstruction in the bile ducts, preventing proper bilirubin excretion. The most common reason for this type of blockage is gallstones, which block the bile ducts. Other causes include tumors in the pancreas or bile ducts, strictures (narrowing) of the bile ducts, or inflammation of the pancreas (pancreatitis). These obstructions cause conjugated bilirubin to back up into the bloodstream, leading to its accumulation.
Recognizing the Signs
When bilirubin levels become too high, they can cause noticeable signs. The most common is jaundice, a yellowish discoloration of the skin and eyes. This yellowing occurs because excess bilirubin deposits in these tissues. Jaundice typically becomes apparent when serum bilirubin levels rise above 2 to 3 milligrams per deciliter (mg/dL).
Beyond the yellowing of the skin and eyes, elevated bilirubin can lead to other indicators. Dark-colored urine can occur because conjugated bilirubin is excreted by the kidneys into the urine. Conversely, stools may appear pale or clay-colored due to the reduced amount of bilirubin reaching the intestines.
Generalized itching is another common symptom. Other non-specific symptoms may include fatigue, nausea, vomiting, or abdominal pain. If any of these signs are observed, particularly jaundice, seeking medical attention is important to determine the underlying cause.
What to Do About Elevated Bilirubin
Addressing elevated bilirubin levels involves identifying and treating the specific underlying cause. A healthcare professional will typically begin with a detailed medical history and physical examination. This initial assessment is followed by blood tests to measure total bilirubin, as well as unconjugated and conjugated bilirubin levels. The ratio of these two types helps guide the diagnosis.
Further diagnostic tests may include a complete blood count, liver function tests that measure liver enzymes, and imaging studies such as an abdominal ultrasound or computed tomography (CT) scan. These tests help differentiate between issues occurring before, within, or after the liver. For instance, if the majority of elevated bilirubin is unconjugated and there’s no evidence of red blood cell breakdown, Gilbert’s syndrome is a common, benign cause.
However, if conjugated bilirubin is significantly elevated, it often points to liver disease or bile duct obstruction, necessitating further evaluation. Treatment approaches vary widely depending on the diagnosis, ranging from managing hemolytic conditions with medications to surgical intervention for gallstones or other blockages. Avoiding alcohol and certain medications that can affect the liver, along with maintaining hydration and a balanced diet, can support liver function during the evaluation process.