Bilirubin is a yellowish pigment found in bile, a digestive fluid produced by the liver. It forms as a natural byproduct when old red blood cells break down. Elevated levels of bilirubin, a condition known as hyperbilirubinemia, often manifest as jaundice, causing a yellow discoloration of the skin and eyes. High bilirubin is not a disease itself, but rather an indicator of an underlying issue that requires investigation.
How Bilirubin is Processed
The journey of bilirubin begins with the breakdown of aged red blood cells, primarily in the spleen. Hemoglobin, the oxygen-carrying protein, is converted into unconjugated (indirect) bilirubin. This initial form is not water-soluble and binds to albumin for transport through the bloodstream to the liver.
Once it reaches the liver, unconjugated bilirubin undergoes a transformation. Liver cells process it by attaching it to a sugar molecule, a process called conjugation. This converts it into water-soluble conjugated (direct) bilirubin. Conjugated bilirubin is then excreted from the liver into bile, passing into the small intestine. In the intestines, bacteria metabolize it, leading to its elimination largely through feces, giving stool its characteristic brown color.
Conditions Causing Increased Red Blood Cell Breakdown
High bilirubin levels can stem from conditions that cause an excessive breakdown of red blood cells, overwhelming the liver’s capacity to process the resulting bilirubin. This leads to an accumulation of unconjugated bilirubin in the bloodstream. These are often referred to as “pre-hepatic” causes.
One such condition is hemolytic anemia, where red blood cells are destroyed faster than the body can produce them. Examples include autoimmune hemolytic anemia, or genetic conditions like sickle cell anemia and thalassemia. The sheer volume of bilirubin produced from rapid red blood cell destruction exceeds the liver’s ability to conjugate it efficiently.
Large hematomas, collections of blood outside blood vessels, can also contribute to elevated bilirubin. As the body reabsorbs blood from a significant bruise or internal bleeding, the breakdown of these red blood cells generates a substantial amount of bilirubin. Similarly, ineffective erythropoiesis, a condition where red blood cell production in the bone marrow is faulty, results in the early destruction of developing red cells. This premature destruction also contributes to an increased load of unconjugated bilirubin.
Conditions Affecting Liver Processing
Issues directly impacting the liver’s ability to handle bilirubin can also lead to elevated levels. This category, known as “hepatic” causes, can result in high unconjugated, conjugated, or mixed bilirubin, depending on the specific liver impairment.
Inflammation of the liver, or hepatitis, can significantly impair its function. This inflammation, whether from viral infections (like hepatitis A, B, or C), excessive alcohol consumption, certain medications, or autoimmune responses, reduces the liver’s capacity to process bilirubin effectively. Over time, chronic liver inflammation can lead to cirrhosis, a severe scarring of the liver tissue. Cirrhosis diminishes the liver’s ability to clear bilirubin and other waste products from the blood.
Genetic conditions can also affect liver processing. Gilbert’s syndrome is a common, often harmless genetic disorder where the liver has a reduced ability to conjugate bilirubin. This leads to mild, intermittent increases in unconjugated bilirubin. Rarer genetic disorders, such as Crigler-Najjar syndrome and Dubin-Johnson syndrome, involve more severe defects in bilirubin processing. Crigler-Najjar syndrome involves a significant reduction or absence of the enzyme needed for bilirubin conjugation, leading to high unconjugated bilirubin that can be life-threatening. Dubin-Johnson syndrome, on the other hand, involves a defect in the liver’s ability to excrete conjugated bilirubin into bile, causing an accumulation of conjugated bilirubin.
Conditions Blocking Bile Flow
Bilirubin levels can rise when there is an obstruction preventing the proper flow of conjugated bilirubin from the liver through the bile ducts. These are termed “post-hepatic” or “obstructive” causes, and they primarily result in elevated conjugated bilirubin. The blockage causes bile to back up into the bloodstream.
Gallstones are a frequent cause of such obstructions. These hardened deposits can form in the gallbladder and then move into the bile ducts, blocking the pathway for bile to reach the small intestine. Tumors, whether originating in the pancreas, bile ducts, or liver, can also compress or directly block the bile ducts. This physical obstruction prevents the normal drainage of bile.
Bile duct strictures, narrowings of the bile ducts, can also impede bile flow. These strictures can develop due to inflammation, injury, or other causes, creating a bottleneck for bilirubin excretion. Pancreatitis, a severe inflammation of the pancreas, can cause swelling of the pancreatic head, which may then compress the common bile duct. Autoimmune diseases like Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC) damage the bile ducts, leading to inflammation and scarring that obstruct bile flow.
High Bilirubin in Newborns
Elevated bilirubin levels are common in newborns, often manifesting as jaundice. This is frequently a temporary and expected phenomenon, referred to as physiological jaundice. Newborns have a higher turnover of red blood cells compared to adults, meaning more bilirubin is produced. Additionally, their livers are still developing and are not yet fully efficient at processing and conjugating bilirubin, leading to a temporary buildup. This type of jaundice typically resolves on its own within the first week of life.
Sometimes, breastfeeding practices can contribute to high bilirubin levels. Breastfeeding jaundice can occur if a newborn is not receiving enough milk, leading to dehydration and reduced bilirubin elimination. Another form, breast milk jaundice, is thought to be caused by certain substances in breast milk that can interfere with bilirubin processing and reabsorption in the infant’s intestines. In some cases, blood group incompatibility between the mother and baby, such as ABO or Rh incompatibility, can lead to increased red blood cell breakdown in the newborn. This heightened destruction results in a larger load of unconjugated bilirubin for the immature liver to handle, potentially causing more pronounced jaundice.