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Bilirubin

Updated : July 9, 2024


Bilirubin is the red orange compound. It breaks down the heme – a necessary process for the body’s waste product. Hemoglobin molecules produce the bilirubin. Heme converts to biliverdin by enzyme biliverdin reductase. Biliverdin converts to bilirubin. Body breaks the bilirubin and eliminate by bile and urine. Bilirubin origin metabolites like urobilin and stercobilin. These cause yellow urine and brown stool. Bilirubin is insoluble in water in that not conjugated form. This type of bilirubin binds to the albumin in plasma and restricts its distribution to the vascular space. This will not undergo filtration by the kidney glomerular filtration. The albumin – bilirubin complex separates in the liver. By the help of the hepatocytes, it is converted into uridine diphosphoglucuronate glucuronosyltransferase (UGT). It is water soluble in nature. Bilirubin in the conjugated form enters into small intestine in discharged bile. This form is predominant in nature (80 % – 85 %). Bilirubin in the conjugated form enters into small intestine in discharged bile. Bilirubin converts into urobilinogen by intestinal bacteria. Intestines reabsorb the urobilinogen and return to liver by enyterohepatic circulation. The major part is expelled in stool. A minor part is excreted in urine. These is the reason of the yellow color of urine and brown color of stool. When urobilinogen is absent, in that case urine lose its normal color. The stool looks like clay color. 

Bilirubin is the red orange compound. It breaks down the heme – a necessary process for the body’s waste product. Hemoglobin molecules produce the bilirubin. Heme converts to biliverdin by enzyme biliverdin reductase. Biliverdin converts to bilirubin. Body breaks the bilirubin and eliminate by bile and urine. Bilirubin origin metabolites like urobilin and stercobilin. These cause yellow urine and brown stool. Bilirubin is insoluble in water in that not conjugated form. This type of bilirubin binds to the albumin in plasma and restricts its distribution to the vascular space. This will not undergo filtration by the kidney glomerular filtration. The albumin – bilirubin complex separates in the liver. By the help of the hepatocytes, it is converted into uridine diphosphoglucuronate glucuronosyltransferase (UGT). It is water soluble in nature. Bilirubin in the conjugated form enters into small intestine in discharged bile. This form is predominant in nature (80 % – 85 %). Bilirubin in the conjugated form enters into small intestine in discharged bile. Bilirubin converts into urobilinogen by intestinal bacteria. Intestines reabsorb the urobilinogen and return to liver by enyterohepatic circulation. The major part is expelled in stool. A minor part is excreted in urine. These is the reason of the yellow color of urine and brown color of stool. When urobilinogen is absent, in that case urine lose its normal color. The stool looks like clay color. 

The abnormal range of bilirubin may indicate liver or bile duct issues. Increased bilirubin concentrations may stem from an augmented degradation of RBC. 

Bilirubin test is performed in the below conditions: 

Jaundice 

Anemia 

Adverse reaction to drug 

Alcohol consumption 

Contact to hepatitis virus 

Cirrhosis 

Bilirubin test is performed if you experience symptoms: 

Nausea 

Vomiting 

Pain 

Dark urine color 

Heartburn 

Constipation 

Yellow eye and skin 

Loss of appetite 

Fever 

Fatigue

Clinical Significance: 

In jaundice and prolonged cholestasis, there is absence of bilirubinuria. This is occurred due to tight bond of direct bilirubin and albumin in blood serum. 

Unconjugated hyperbilirubinemia: Increased level of unconjugated bilirubin does not appear in urine. Urine is not affected in jaundice with Acholuric. 

Conjugated hyperbilirubinemia: Urine dark in color indicate excretion of conjugated bilirubin. This leads to the liver or biliary disorders.  

Glomerular disease: Unconjugated bilirubin with albumin is not able to pass the kidney glomerular filtration. 

 

  • Normal bilirubin range:  
  • Adult/Geriatric/Pediatric:  
  • Total bilirubin: 0.3 mg/dL – 1.0 mg/dL 
  • Indirect (unconjugated) bilirubin: 0.2 mg/dL – 0.8 mg/dL 
  • Direct (conjugated) bilirubin: 0.1 mg/dL – 0.3 mg/dL 
  • Newborn: 
  • Total bilirubin: 1.0 mg/dL – 12.0 mg/dL 
  • The mean total bilirubin level in the 176 million human being in United states:  
  • Men: 0.72 mg/dL  
  • Women: 0.52 mg/dL  
  • Overall: 0.62 mg/dL  
  • Critical bilirubin range:   
  • Newborns: Total bilirubin level = Greater than 15 mg/dL in the first 48 hours or 20 mg/dL after 72 hours.  
  • Adult: Total bilirubin = Greater than 12 mg/dL  

  • Conjugated hyperbilirubinemia and unconjugated hyperbilirubinemia occur due to: 
  • Conjugated hyperbilirubinemia: 
  • Intrahepatic: 
  • Liver filteration disease (Tuberculosis, Amyloidosis, Sarcoidosis, Lymphoma) 
  • Parasite infections 
  • Alcoholic hepatitis, Viral hepatitis: Hepatitis A-E, Autoimmune hepatitis 
  • Intrahepatic cholestasis of pregnancy  
  • Sickle cell disease  
  • Cirrhosis  
  • Extrahepatic: 
  • Biliary obstruction like: 
  • Choledochal cysts 
  • Pancreatitis (chronic and acute) 
  • Biliary strictures 
  • Choledochal cyst 
  • Primary sclerosing cholangitis 
  • Parasite infection 
  • AIDS cholangiopathy 
  • Inherited disorders like Rotor syndrome, Dubin-Johnson syndrome (DJS), Caroli disease 
  • Inherited Conditions like Dubin-Johnson syndrome (DJS), Rotor syndrome, Benign recurrent intrahepatic cholestasis (BRIC), Wilson disease 
  • Drugs like,  
  • Isoniazid 
  • Chlorpromazine 
  • Erythromycin 
  • Anabolic steroids 
  • Other factors like: 
  • Sepsis 
  • Shock 
  • Hemochromatosis 
  • Unconjugated hyperbilirubinemia: 
  • The three primary pathophysiological conditions:  
  • Elevated bilirubin production 
  • Defective bilirubin conjugation 
  • Decreased hepatic clearance 
  • Collection and Panels:  

Sample type: Plasma or serum 

Sample collection conatiner: 0.5 mL of plasma using a green-top (heparin) tube or 0.7 mL of serum using a red-top tube or a 7-mL SST (gold-top) tube.  

Storage requirements: Store the sample for 2 days at room temperature, 3 days in refrigerator, 14 days if you freeze the sample. 

Considerations: Fasting for at least four hours before testing. Discontinuing drugs before the test which affect the result. 

Panels:  

Comprehensive metabolic panel (CMP) 

Hepatic function panel (HFPA) 

Modifying factors: 

Medications elevate the bilirubin level in the blood: certain antibiotics, antimalarials, oral contraceptives, morphine, some steroids, and monoamine oxidase (MAO) inhibitors.  

Medications reduce the bilirubin level in the blood: high-dose salicylates, penicillin, caffeine, and barbiturates.  

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