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.
تعليقات
إرسال تعليق