Total Bilirubin

Bilirubin, a yellowish pigment produced during the breakdown of red blood cells, serves as a vital marker of liver function and blood health. Within the bloodstream, bilirubin exists in two main forms: indirect (unconjugated) and direct (conjugated) bilirubin. 

Total bilirubin is the sum of direct and indirect bilirubin.

Indirect bilirubin must be converted to direct bilirubin to be excreted by the kidneys. 

Direct bilirubin, a water-soluble form, is a key component of liver function tests and serves as a crucial indicator of liver and biliary tract health. Elevated levels of direct bilirubin can signify liver disease, bile duct obstruction, or other hepatobiliary disorders. 

Understanding the clinical significance of total bilirubin as a blood test is essential for diagnosing and managing various medical conditions related to liver function and biliary tract integrity.

What is Bilirubin?

Bilirubin is a yellowish pigment produced by the breakdown of heme, a component of hemoglobin found in red blood cells. 

As a byproduct of heme metabolism, bilirubin is primarily derived from the breakdown of hemoglobin in senescent red blood cells and other heme-containing proteins. This process occurs mainly in the reticuloendothelial system of the spleen, although it also occurs in phagocytes and Kupffer cells in the liver. 

This unconjugated bilirubin is then released into circulation where, as an insoluble molecule, it must bind to albumin to travel through the bloodstream.  Unconjugated bilirubin travels to the liver where it is conjugated, becoming direct bilirubin via conjugation.  

In the liver, bilirubin is conjugated with glucuronic acid, which renders it water-soluble and allows it to be excreted into bile. From there, bilirubin travels through the biliary tract to the intestines, where it undergoes further metabolism by gut bacteria and is ultimately eliminated from the body through feces.  

Conjugated bilirubin is not reabsorbed, although a portion of unconjugated bilirubin may be reabsorbed in the intestines.  [6.]

This process is essential for the safe detoxification and elimination of bilirubin from the body, preventing its accumulation and potential toxicity.

When the liver cannot process bilirubin quickly enough, it begins to build up in the body and is eliminated via the urine.

Because bilirubin is primarily made in the liver as a byproduct of red blood cell breakdown and serves as an important marker of liver function and overall blood health.

Differentiating Direct and Indirect Bilirubin from Total Bilirubin [6.] 

Total bilirubin represents the combined levels of both indirect (unconjugated) and direct (conjugated) bilirubin in the bloodstream. While total bilirubin provides an overall measure of bilirubin concentration, direct bilirubin specifically reflects the fraction of bilirubin that has undergone conjugation in the liver. 

By differentiating between direct and indirect bilirubin levels, clinicians can gain valuable insights into the underlying etiology of elevated bilirubin levels. 

Elevated direct bilirubin levels suggest hepatobiliary dysfunction, while elevated indirect bilirubin levels may indicate increased hemolysis or impaired hepatic uptake. Therefore, understanding the distinction between direct, indirect and total bilirubin levels is essential for accurate diagnosis and appropriate management of liver and biliary tract disorders.

Testing Total Bilirubin

Sample Requirements and Test Procedure

The total bilirubin test may be done through blood or urine.  

Total bilirubin is typically part of routine blood work called a comprehensive metabolic panel.  A blood test typically requires a blood sample obtained through venipuncture, where a healthcare professional collects blood from a vein in the arm using a sterile needle and syringe or a vacuum tube system. 

During a urine test for bilirubin, a urine sample is collected and analyzed using a dipstick or laboratory equipment to detect the presence of bilirubin. The test involves dipping a specially treated strip into the urine sample which reacts with bilirubin, causing a color change that indicates its presence in the urine, aiding in the diagnosis of liver or biliary tract disorders.

Fasting is not generally required, although your healthcare provider may request fasting especially if this test is ordered in conjunction with other tests.  

Bilirubin Reference Ranges

Reference ranges for bilirubin may differ based on a person’s age, and they also may differ between labs.  

Serum Values [6.]

Serum values of total bilirubin for an adult: 

Total bilirubin: 0.3-1.0 mg/dL or 5.1-17 μmol/L (SI units)

Urine Values  [7.] 

In urine, the presence of bilirubin is considered abnormal, and its detection may suggest liver or biliary tract dysfunction, regardless of specific quantitative reference ranges.

Abnormalities in total bilirubin levels in blood or urine may require additional testing to determine whether the bilirubin present is direct or indirect.  

What Does High Total Bilirubin Mean?

Clinical Implications of Elevated Total Bilirubin Levels

A finding of elevated total bilirubin requires further testing to determine if the direct or direct bilirubin levels, or both, are elevated.  

Elevated Direct Bilirubin  [5.] 

Elevated levels of direct bilirubin in the bloodstream or urine may indicate hepatobiliary dysfunction and liver disease. Direct bilirubin is primarily excreted into bile by the liver, and increased levels in blood and/or urine suggest impairment in bilirubin metabolism, conjugation, or excretion. 

Consequently, elevated direct bilirubin levels are often associated with conditions such as cholestasis, bile duct obstruction, hepatitis, cirrhosis, or other hepatobiliary disorders, necessitating further evaluation and management.

Elevated Indirect Bilirubin  [10.]

Elevated levels of indirect bilirubin can result from various factors affecting the production, metabolism, or excretion of bilirubin. 

Conditions associated with hemolysis, or the increased breakdown of red blood cells, can lead to an excess of bilirubin formation. Additionally, liver diseases that impair the uptake, conjugation, or excretion of bilirubin, such as Gilbert syndrome or Crigler-Najjar syndrome, can elevate indirect bilirubin levels. 

Disorders affecting heme metabolism, such as ineffective erythropoiesis or increased bilirubin production from other heme-containing proteins, can also contribute to elevated indirect bilirubin. 

Furthermore, certain medications or substances, like rifampin or fasting, may interfere with bilirubin metabolism and lead to its accumulation. 

What Causes High Bilirubin in Newborns?

Neonatal Jaundice: Etiology and Pathophysiology  [1., 9.]

Neonatal jaundice, characterized by yellowing of the skin and eyes in newborn infants, occurs due to the accumulation of bilirubin in the bloodstream. In newborns, jaundice commonly occurs within the first few days of life due to physiological immaturity of the liver, resulting in decreased bilirubin conjugation and clearance. 

Under normal circumstances, bilirubin is primarily metabolized and excreted by the liver, but in newborns, immature hepatic enzyme systems may lead to inadequate bilirubin processing, causing its accumulation in the bloodstream. 

This excess bilirubin can cross the blood-brain barrier and cause neurotoxicity, leading to kernicterus, a severe neurological condition if left untreated.

Factors Contributing to Elevated Bilirubin Levels in Newborns  [1., 9.]

Several factors contribute to elevated direct bilirubin levels in newborns, leading to neonatal jaundice. These factors include physiological jaundice, which is a common and benign condition resulting from the immature liver function and increased red blood cell breakdown in newborns. 

Additionally, breastfeeding jaundice may occur due to inadequate milk intake, leading to dehydration and decreased bilirubin excretion. Furthermore, breast milk jaundice can arise from substances in breast milk that inhibit bilirubin conjugation in the liver. 

In some cases, pathological causes such as hemolytic disease of the newborn, ABO or Rh incompatibility, or genetic disorders affecting bilirubin metabolism may contribute to elevated direct bilirubin levels and require prompt evaluation and management by healthcare professionals.

Natural Support for Elevated Direct Bilirubin

Understanding and treating the cause of elevated bilirubin is essential.  Under the guidance of a medical professional, an individual treatment plan can be created.  Natural support for elevated bilirubin may include:

Dietary Modifications [12.]

• Increase consumption of foods rich in antioxidants such as fruits, vegetables, and whole grains to support liver function and reduce oxidative stress.

• Incorporate foods high in fiber like legumes, nuts, and seeds to promote regular bowel movements and enhance bilirubin excretion.

Lifestyle Changes

• Maintain hydration by drinking an adequate amount of water throughout the day to support liver and kidney function and regular bowel movements, facilitating bilirubin elimination.

• Engage in regular physical activity to promote blood circulation, enhance liver detoxification processes, and promote regular bowel movements.  [3.]

Supplements

• Milk thistle: consider supplementation with milk thistle extract, known for its hepatoprotective properties and ability to support liver health.  [4.]

• Dandelion root: dandelion root supplements may aid in bile flow and liver detoxification, potentially reducing bilirubin levels.  [8.]

• Turmeric: turmeric supplements containing curcumin, a potent antioxidant, may help reduce inflammation and support liver function, contributing to bilirubin metabolism and excretion. [2.]

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