CLINICAL CHEMISTRY-2 (MLT 302)

LIVER FUNCTION AND THE

BILIARY TRACT
LECTURE THREE
Dr. Essam H. Aljiffri

Jaundice
Bilirubin is a yellow pigment which causes discoloration
of the skin and when serum levels exceed 35-40 mol/L.
Concentrations may increase for three reasons:
- the production rate of bilirubin is increased, exceeding
the excretory capacity of the liver (prehepatic jaundice);
- conjugating and / or excretory functions are reduced, (hepatic
or hepatocellular jaundice);
- biliary obstruction interferes with the flow of bile and thus
bilirubin excretion (posthepatic, obstructive or
cholestatic jaundice).
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Pathogenesis of Jaundice

Prehepatic Jaundice
Prehepatic jaundice is caused by increased destruction
of erythrocytes either:
- mature cells or
- precursors (ineffective erythropoiesis).
The breakdown of mature cells can be caused by:
- haemolysis, or
- as a result of the metabolism of blood
following internal haemorrhage, e.g. into
a soft tissue injury or fracture.
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Prehepatic Jaundice
Ineffective erythropoiesis occurs in conditions such as:
- pernicious anaemia, where the
maturation of red cells is impaired, or
- thalassaemia, where the structure
of haemoglobin is abnormal.
Hyperbilirubinaemia in prehepatic jaundice results from
the accumulation of unconjugated bilirubin; this is not
excreted by the kidney.
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Prehepatic Jaundice
Jaundice occurs because the conjugating capacity of the
liver is saturated,
- the capacity of the liver for conjugation is
greater than the normal rate of bilirubin production.
Increased fluxes of bilirubin through the liver into the gut
Greater amounts of urobilinogen are produced, with
- increased urobilinogen excretion in urine.
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KEY POINTS
Prehepatic jaundice is most commonly
Caused by haemolytic disease

Bilirubin (unconjugated) is not excreted in urine

Urinary urobilinogen concentration is increased

Hepatic Jaundice
Congenital disorders of bilirubin transport lead to
jaundice because of:
- defective uptake, reduced conjugation
or impaired excretion of bilirubin.
Generalized hepatocellular dysfunction may
occur in hepatitis and hepatic cirrhosis.
Drugs may cause hepatocellular damage, either
due to dose-dependent hepatoxicity (e.g.
paracetamol).
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Hepatic Jaundice
The pathogenesis of jaundice in these
conditions is complex,
- reduced hepatic uptake,
- decreased conjugation and,
- impaired intracellular transport
of bilirubin, all contributing.

Hepatic Jaundice
When hyperbilirubinaemia is caused by impaired
conjugation of bilirubin;
- unconjugated bilirubin, and no
increased fluxes of bilirubin through the liver,
- bilirubinuria does not occur and
- urinary urobilinogen is not increased.
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Hepatic Jaundice
Serum bilirubin may be unconjugated or conjugated, as
UDP glucuronyl transferase and intracellular transport
may be defective.
If the rate of conjugation exceeds excretory capacity;
- conjugated hyperbilirubinaemia will
occur and bilirubin may be excreted,in urine,
- this is sometimes seen in recovery from acute
viral hepatitis.
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KEY POINTS
Jaundice due to hepatocyte dysfunction may be
caused by selective transport defects
of generalized cell dysfunction
Both conjugated and unconjugated hyperbilrubinaemia
may occur in hepatocellular jaundice

Bilirubin and excess urobilinogen may be

found in urine
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Cholestatic Jaundice
Cholestatic jaundice results from interference to biliary
flow between the sites of secretion by the hepatocyte
and drainage into the duodenum.
It may be caused by lesions;
- within the liver (intrahepatic cholestasis),
or in the biliary tree or head of the
pancreas (extrahepatic cholestasis);
- the term cholestatic is preferable to post-hepatic
to describe this pattern of jaundice.
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Cholestatic Jaundice

Intra- and extra-hepatic cholestasis can be differentiated by;

- ultrasound examination or
- liver biopsy, but not by liver function tests.

Intrahepatic cholestasis may result from generalized hepatocellular

dysfunction, such as occurs in;
- Hepatitis,
- Hepatic cirrhosis

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Hepatic malignancies may block branches of the biliary tree.

Cholestatic Jaundice
Some drugs may cause intrahepatic cholestasis such as:
- anabolic steroids, and
- phenothiazines
Extrahepatic obstruction may be due to tumours in:
- major branches of the biliary tract,
- head of pancreas.
Gallstones may obstruct biliary flow.
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Cholestatic Jaundice
Jaundice is due to impaired excretion and
accumulation of conjugated bilirubin which can
be filtered by the kidney and appear in urine.
If obstruction is complete bilirubin does not
reach the gut, therefore urobilinogen:
- is not produced, and
- is absent in urine.
Under such circumstances the stools are pale.
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KEY POINTS
Cholestasis may be caused by lesions
within or outside the liver

Jaundice is due to conjugated bilirubin

Bilirubin is found in urine

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Summary in liver function tests in the

differential diagnosis of jaundice

Test

Prehepatic

Hepatic

Serum bilirubin Uncojugated

Urine bilirubin

ALP

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Mixed Conjugated

Absent//PresentPresent Present

Urine Urobilinogen
ALT & AST
increase

Cholestatic

Increased

Increased

Decreased

increase

increase

Normal Marked Slight

increase

Normal Slight

Marked