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Liver function tests: hepatic excretory function evaluation

 
Liver function tests: hepatic excretory function evaluation

Tests for evaluation of hepatic excretory function

The liver is responsible for excretion some substances from the body including cholesterol and foreign substances to biliary tract as well as the liver cells are responsible for conjugation of bilirubin and its excretion into the biliary tract.

For hepatic excretory function evaluation, we measure serum total serum cholesterol especially in state of obstructive jaundice (Cholestasis). The most common investigations for hepatic excretory function evaluation are serum total bilirubin and serum direct bilirubin measurement.

Bilirubin metabolism

The sources of bilirubin in the body are hemoglobin, myoglobin and cytochromes. Formation and degradation of bilirubin occur as the following:

a) In the blood circulation:

1. In the body, the bilirubin is produced from haemoglobin released by destruction of RBCs in the reticuloendothelial system.

2. In the blood circulation, bilirubin binds with albumin forming albumin-bilirubin complex called unconjugated bilirubin (free, unbound and indirect bilirubin) which is water insoluble(lipophilic) and cannot excreted in the urine.

3. The unconjugated bilirubin are transported to the liver.

b) In the liver

1. The unconjugated bilirubin (albumin-bilirubin complex) enters the liver.

2. Then bilirubin within the hepatic cell is conjugated with two molecules of glucuronic acid by uridine diphosphate(UDP) glucuronyl transferase forming conjugated bilirubin (bilirubin glucuronides).

3. The conjugated bilirubin is water soluble and appears in urine if it is increased in the blood.

4. Excretion of bilirubin into bile The conjugated bilirubin is excreted into the bile canaliculi, then enters the bile.

d) Fate of bilirubin

 1. The conjugated bilirubin (bilirubin diglucuronide) in the intestine is cleaved by specific bacterial enzymes called β-glucuronidase liberating bilirubin.

 2. The bilirubin in the intestine is converted to urobilinogen.

3. Small amount of urobilinogen is reabsorbed into systemic circulation where it is converted to urobilin in the kidney and is excreted in the urine.

Jaundice

 Jaundice is yellow-orange discoloration of the skin due to a high plasma concentration of bilirubin in which total plasma bilirubin exceeds about 2 mg/dl (normally 0.3──1.0 mg/dl).

Clinical significant of bilirubin determination

Serum total and direct bilirubin determinations are used for the diagnosis, differentiation and follow up of jaundice.

Jaundice classification

Generally, jaundice is classified into three types namely hemolytic, hepatic, and obstructive.

1.       Pre-hepatic (hemolytic jaundice)

2.       Hepatic (Hepatocellular jaundice)

3.       Post-Hepatic (Cholestatic or obstructive jaundice)

Prehepatic (hemolytic jaundice)

This is due to increased hemolysis of erythrocytes and failure in conjugate or transport of bilirubin across the parenchymal cells.

· Hemolytic anemia e.g. sickle cell anemia, spherocytosis, glucose-6-dehydrogenas deficiency, thalassaemia and incompatible blood transfusion.

 · Gilbertۥs disease

This disease is asymptomatic and causes increased unconjugated bilirubin after attack of hepatitis or any mild illness. This disease is inheritance, harmless and is caused by: 1. A defect in uptake of bilirubin by liver cells. 2. An impairment of bilirubin conjugation due to reduced activity of UDP-glucuronyltransferase. 3. Decreased hepatic clearance of bilirubin.

 · Crigler-Najjar syndrome

 It is a serious condition and may be fatal which is inherited as autosomal recessive. This disease is due to deficiency of UDP-glucuronyltransferase. It may lead to Kernicterus and death.

Hepatic (Hepatocellular jaundice)

This is caused by dysfunction of the liver due to damage of the parenchymal cells which decreases bilirubin uptake and its conjugation by liver cells. The causes of hepatic jaundice include:

 - Viral infections (viral hepatitis)

- Toxins such as alcohol.

- Liver cirrhosis.

 

Post-Hepatic (Cholestatic or obstructive jaundice)

This is due to an obstruction of the bile duct that prevents the passage of bile into the intestine leading to entrance of conjugated bilirubin into the circulation.

 

Hyperbilirubinemia

Causes of unconjugated(indirect) Hyperbilirubinemia

1. Hemolytic anemia e.g. hemoglobinpathies and incompatible blood transfusion.

2. Gilbert' s syndrome.

3. malaria

5. Inborn and premature infants.

6. Crigler-Najjar syndrome.

 

 II. Causes of conjugated(direct) Hyperbilirubinemia

1. Dubin-Johnson syndrome.

2. Rotor syndrome.

3. Cirrhosis (Occasionally)

4. Hepatitis (Often)

5. Alcoholic liver disease (Occasionally)

7. Primary biliary cirrhosis.

8. Gall stones

9. Carcinoma of bile duct and pancreas.

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