Bilirubin - Production and Metabolism

Introduction

Bilirubin, also known as bile pigment, is produced by the liver. Bile is a yellowish-green fluid that gives the gallbladder the same color. The gallbladder (a gland attached to the liver) stores bilirubin. The gallbladder stores and concentrates bile secreted by the liver. It provides a reservoir for bitterness. Bile is carried from the liver by the bile duct. The liver plays a crucial role in the production and metabolism of bilirubin. The liver secretes one to two liters of bile per day. Bilirubin exists in two forms - unconjugated and conjugated forms. Bile lacks enzymes and contains bile acids formed by cholesterol, phospholipids, and bilirubin. This article explains the types, functions, and metabolism of bilirubin, along with the clinical significance of bilirubin levels in our bodies.

What Is Bilirubin?

The liver secretes bile. Bile consists of two pigments - bilirubin and biliverdin. Bile also consists of water and solids. Normal bilirubin (total bilirubin) content in the plasma is 0.5 to 1.5 milligrams per deciliter. Bile secretion is a continuous process, and its production decreases under fasting conditions. However, it starts increasing after meals and continues for three hours. The properties of bile are:

• Volume - 800 to 1200 milliliters/day.

• Reaction - Alkaline.

• Specific Gravity - 1.010 to 1.011.

• pH (Potential of Hydrogen) - 8 to 8.6.

• Color - Golden, yellow, or green.

What Are the Types of Bilirubin?

The following are the two types of bilirubin:

• Unconjugated Bilirubin - The bilirubin which is not soluble in water and bound to the albumin protein is called unconjugated bilirubin. It does not pass-through urine. Almost all bilirubin in the blood is unconjugated. Around 250 mg to 300 milligrams of unconjugated bilirubin is produced from the catabolism of heme (a component of hemoglobin in the blood) daily.

• Conjugated Bilirubin - The bilirubin soluble in water is called conjugated bilirubin. Colonic bacteria metabolize conjugated bilirubin, and it is excreted in the bile.

What Is the Composition of Bile?

Bile contains 97.6 percent water and 2.4 percent solids. Solids include organic and inorganic substances. The composition of bile is explained below:

What Are the Functions of Bile?

The functions of bile are detailed below:

Digestive Functions - Bile is composed of bile salt and is required to digest fats in the intestine. Bile helps in the digestion of fats by a process called emulsification. Emulsification is the process by which the bigger fat molecules are broken down into smaller fat molecules. These smaller fat molecules are made from milky fluids called emulsions. The emulsification of fat takes place in the small intestine by the actions of bile salts. More giant fat molecules are insoluble in water. Hence, the gastrointestinal tract cannot digest the fat directly. Bile salts play a vital role in the digestion of fats. The undigested bigger fat molecules usually pass through the intestine, which is then eliminated in feces.

Absorptive Functions - Bile helps absorb digested fat from the intestine into the blood. The form of micelles (a complex of fats formed by the combination of bile salts and fats) can be absorbed easily.

Laxative Functions - Laxative is an agent that helps in defecation (excretion in the form of feces). Bile salts act as laxatives by stimulating the peristaltic movement of the intestine.

Antiseptic Action - Bile inhibits the growth of certain bacteria in the intestine by its natural detergent action.

Lubrication Function - Bile (mucin in bile) acts as a lubricant for food in the intestine during digestion.

Maintenance of the pH in Gastrointestinal Tract - As bile is highly basic, it neutralizes the acid which enters the intestine from the stomach. Bile helps maintain an optimum pH for digestion in the stomach.

Prevention of Gallstones Formation - Bile salt is present in bile to prevent the formation of gallstones by keeping the cholesterol and lecithin in solution. In the absence of bile salt, cholesterol precipitates along with less than uniform gallstone.

Excretory Functions - Bile pigments are the primary excretory product of bile. Some substances excreted in bile are metals (copper and iron), some bacteria (typhoid bacteria), toxins, and cholesterol.

How Is Bilirubin Produced?

Bilirubin is formed when hemoglobin is broken down from destroyed red blood cells in the reticuloendothelial system. The following are the stages in the formation of bilirubin:

• Following the degradation of red blood cells. Hemoglobin is liberated.

• Hemoglobin is divided into two components heme and globin (proteins responsible for binding oxygen).

• Heme is divided into two components iron and bile pigment (biliverdin).

• First-formed pigment biliverdin is reduced to bilirubin.

• Bilirubin is released into the blood.

• In blood, the bilirubin is circulated (unconjugated bilirubin).

• The liver cell takes up the unconjugated bilirubin (free bilirubin) within a few hours after entering circulation.

• The liver attaches to acid to form indirect bilirubin (conjugated bilirubin).

How Is Bilirubin Metabolized?

The metabolism of bilirubin takes place in three steps:

Production of Bilirubin

• The process of hemolysis produces bilirubin.

• Hemolysis is the process of metabolism of red blood cells.

• The metabolism of hemoglobin produces bilirubin. Hemoglobin is broken down into the components - heme and globin.

• Globin is further broken down into amino acids and recycled.

• Heme is broken down into two components, iron, and biliverdin.

Transportation of Bilirubin

• Bile is produced by the liver and stored by the gallbladder.

• Bile is carried from the liver by the bile duct, called ductus choledochus.

• It is formed by the union of the cystic duct from the common hepatic duct and the gallbladder.

• The cystic duct is formed by the union of the right and left hepatic ducts from the corresponding liver lobes.

• The bile duct passes downward and is joined by the pancreatic duct, creating the short hepatopancreatic chimney.

• There are muscles that surround the bile duct before joining the pancreatic duct, and they remain closed in the absence of food in the intestine.

• This forces the ball into the gall bladder via the cystic duct for storage.

Excretion of Bilirubin

The stages of excretion of bilirubin are:

• Bile pigments are the excretory products in the bile.

• Bilirubin and biliverdin are the two pigments present in bile.

• Bilirubin contributes majorly to the bile pigment.

• About 50 percent of the indirect bilirubin (conjugated bilirubin) is converted into urobilinogen in the intestine by intestinal bacteria (colonic bacteria).

• First, the conjugated bilirubin is de-conjugated into the free or unconjugated bilirubin.

• Unconjugated bilirubin is reduced into urobilinogen.

• The remaining 50 percent of the indirect bilirubin is absorbed into the blood from the intestine and enters the liver through the portal vein.

• From the liver, it is re-excreted in bile.

• Almost all urobilinogen reaches the liver from the intestine through blood circulation. Later, it is re-excreted through bile. In contrast, urobilinogen is excreted through urine and feces as stercobilinogen.

• The kidney excretes about five percent of unconjugated bilirubin in the form of urobilinogen.

Conclusion

The liver plays a central role in the metabolism of bilirubin. The liver secretes bile. Bile plays a crucial role in the digestion and absorption of fats. Bile salt is present in bile to prevent the formation of gall stones. In addition, bile inhibits the growth of certain bacteria. Jaundice, liver inflammation (hepatitis), liver cirrhosis, and gallstones can be caused due to abnormal levels of bilirubin. Bile is excreted through the kidney in the form of urobilinogen and stercobilinogen. The advancements in diagnosis and treatment combat bilirubin toxicity, and various treatment protocols limit the acute effect of the high bilirubin level.