Bilirubin Metabolism

What sample is needed for serum bilirubin? 

1. It is done on the patient’s serum.
2. Heparinized plasma can be used.
3. A random sample can be taken.
4. The serum is stable for 3 days at 1 to 6 °C.

What are the precautions for Bilirubin Metabolism?

1. Avoid hemolysis.
2. A fasting sample is preferred for bilirubin.
3. Protect serum or plasma from the light.
4. Lipemia also falsely increased the value.

What are the Indications for serum bilirubin?

1. LFT diagnoses any liver disease.
2. LFT has been done to follow up with the patient on treatment.
3. LFT is done routinely in patients on chemotherapy.
4. LFT may be advised in a patient with treatment on antituberculous treatment.

What tests are included in routine LFT?

1. Bilirubin.
   1. Bilirubin total
   2. Bilirubin is direct and indirect.
2. SGPT.
3. SGOT.
4. Alkaline phosphatase
5. Total protein.
6. Albumin.

What are the additional liver function tests?

1. γ – GT (gamma – GT)
2. Viral hepatitis profiles like HBV, HCV, HAV, HDV, HEV, etc.,

What are the steps in the diagnosis of Jaundice?

1. Clinical history of the patient and examination.
2. Stool examination for ova and parasite.
3. Occult blood in the stool is positive for cancers.
4. Urine examination:
   1. The persistent absence of the urobilinogen indicates obstructive jaundice.
   2. Bilirubinuria is an early sign of viral hepatitis.
   3. Negative urobilinogen and bilirubin indicate hemolytic anemia.
   4. Dark urine and clay-colored stool indicate hepatocellular or cholestatic jaundice.
5. Advise biochemical tests like LFT, serum albumin, alkaline phosphatase, γ-GT, PT, total proteins, and immunoglobulin quantitation.
6. Hematological work-ups like CBC, reticulocytes, and Coomb’s test.
7. Serological tests include ANA, Mitochondrial antibody, IgG, IgA, IgM, hepatitis viral profile, and AFP.
8. Radiology includes X-rays, plain X-ray of the abdomen, USG, and CT scans.
9. Special tests like α1-antitrypsin, amylase, ceruloplasmin, iron, and IBC.
10. Needle biopsy or FNA.

How will you discuss the functions of the liver?

1. The liver is a multifunctional organ involved in various functions, such as excretory, synthesis, detoxification, storage, and metabolism.
2. It can store (storage function):
   1. Amino Acids.
   2. Carbohydrates.
   3. Lipids.
   4. Vitamins.
   5. Minerals.
3. It can synthesize  (metabolic function):
   1. Protein, like albumin, alpha, and beta globulins.
   2. Coagulation factors.
   3. Transport proteins.
   4. Bile acids from cholesterol.
4. The liver is the site for detoxification of:
   1. Drugs.
   2. Toxins.
5. Its major function is Conjugation:
   1. bilirubin combines with glucuronic acid as:
      1. Bilirubin Monoglucuronide.
      2. Bilirubin diglucuronide.
6. The liver has an excretory function:
   1. Excrete bilirubin into bile.
   2. Bile acid is excreted into the bile.
7. The liver is also the site of catabolism of:
   1. Thyroid hormone.
   2. Steroids hormones.
   3. Few other hormones as well.

How will you discuss Bilirubin metabolism?

What are the changes in the mononuclear phagocytic system?

1. The breakdown of the RBCs is a major source for forming Globin and heme.
2. Heme changes into Biliverdin and releases iron, recycled to form RBCs in the bone marrow.
3. Biliverdin forms the unconjugated bilirubin, which is fat-soluble.

Bilirubin Metabolism

What are the changes in the liver cells?

1. Unconjugated bilirubin is in the presence of glucoronyl transferase enzyme conjugated with glucuronic acid.
2. Monoglucuronide and diglucuronide (conjugated bilirubin) are formed.
3. Conjugated bilirubin enters the enterohepatic circulation.
4. Bilirubin 95% is excreted into bile in the form of:
   1. Glucuronide.
      1. ∼90% is diglucuronide.
      2. ∼10% is monoglucuronide.
   2. Glucosides.
   3. Xylosides.

Bilirubin metabolism and excretion

What are the changes of bilirubin in the intestine?

1. Bilirubin is hydrolyzed by the catalytic action of β-glucuronidase from the liver, intestinal epithelial cells, and bacteria.
2. The anaerobic intestinal bacterial flora reduces the unconjugated bilirubin to form a group of three colorless tetrapyrroles called urobilinogen:
   1. Stercobilinogen.
   2. Mesobilinogen.
   3. Urobilinogen, 20%, reabsorbed from the intestine and entered the enterohepatic circulation.

How is Bilirubin excreted in the urine?

1. When bile reaches the duodenum, it is acted by the intestinal bacteria, which will convert most of the bilirubin into urobilinogen.
2. Most urobilinogen is lost in the stool, but part is absorbed into blood circulation.
3. Urobilinogen in the blood travels to the liver (Enterohepatic circulation) and is excreted by the hepatic cells.
4. The kidneys excrete some of this urobilinogen, which appears in the urine.
5. Conjugated bilirubin, like urobilinogen, is partially excreted by the kidneys if the serum level is raised.
6. Unconjugated bilirubin can not pass through the glomeruli, so it does not appear in the urine.
7. In case of an increased level of unconjugated bilirubin, there is an increase in the conjugated bilirubin, which will enter the bile duct and the intestine, and more urobilinogen is produced.
8. This additional urobilinogen is absorbed into the blood circulation and appears in the urine.
9. Urobilinogen is found in the urine when there is increased production of unconjugated bilirubin.

What is the extrahepatic fate of bilirubin?

1. Water-soluble bilirubin is stored in the gallbladder and released into the intestine.
2. Through enterohepatic circulation, it is excreted in the feces and the urine.
   1. In the urine, it is excreted as urobilinogen.
   2. In the stool as stercobilinogen.
   3. The three urobilinogens in the lower intestinal tracts produce bile pigments:
      1. Stercobilin.
      2. Mesobilin
      3. Urobilin.
   4. These are orange-brown and are major pigments of the stool.

How will you define Jaundice?

1. This is defined as the yellow discoloration of the skin and sclera because of the deposition of bile pigments.
2.  It appears when the serum bilirubin level is above 2 mg/dL.
3. Bilirubin is a yellow pigment that is biotransformed in the liver and then excreted in the bile, urine, and stool.

How would you classify Jaundice?

Based on etiology:

1. Pre-hepatic.
2. Hepatic.
3. Posthepatic.

Physiological classification:

1. Unconjugated hyperbilirubinemia (indirect bilirubin).
2. Conjugated hyperbilirubinemia (indirect bilirubin).

How will you discuss Unconjugated hyperbilirubinemia?

What are the causes of unconjugated hyperbilirubinemia?

1. Increased production:
   1. Hemolysis (hemolytic disease of the newborn).
   2. Hereditary.
   3. Acquired.
   4. Ineffective erythropoiesis.
   5. Increased turnover, like in neonates.
   6. Physiologic jaundice of the newborn.
2. Decreased delivery:
   1. Congestive heart failure.
   2. Portacaval shunt.
3. Decreased uptake by the hepatocytes:
   1. Drugs.
   2. Gilbert’s syndrome.
   3. Sepsis.
   4. Fasting.
4. Decreased storage of unconjugated bilirubin:
   1. Fever.
   2. Competitive inhibition.
5. Decreased conjugation:
   1. Physiologic jaundice, e.g., Neonatal jaundice.
   2. Drugs.
   3. Hereditary like Crigler-Najjar syndrome.
      1. Complete enzyme deficiency, Type 1
      2. Partial enzyme deficiency, Type 2
   4. Hepatocellular dysfunction.
   5. Gilbert’s syndrome.

How will you discuss Conjugated Hyperbilirubinemia?

What are the causes of conjugated hyperbilirubinemia?

1. Decreased secretion into bile canaliculi:
   1. Hepatitis.
   2. Cholestasis (Intrahepatic).
   3. Dubin–Johnson syndrome.
   4. Rotor syndrome.
2. Decreased drainage or excretion.
   1. Extrahepatic obstruction:
      1. Stones.
      2. Carcinoma.
      3. Stricture.
      4. Atresia.
      5. Sclerosing cholangitis.
   2. Intrahepatic obstruction:
      1. Drugs.
      2. Primary biliary cirrhosis.
      3. Tumors.
      4. Granulomas.
      5. Idiopathic neonatal hepatitis (cholestatic jaundice).

How will you discuss the characteristics of the various types of jaundice?

What are the causes of Jaundice?

How will you define Hepatorenal failure?

1. There is a progressive renal failure in patients with severe end-stage liver disease (acute liver failure).
2. There is no obvious cause of renal disease.
3. The renal biopsy is essentially normal.

Questions and answers: