cases

Liver function tests
Most laboratories perform a standard group of tests (Table 13.1), which do not assess genuine
liver func- tion but are useful for:

1 Detecting the presence of liver disease.
2 Placing the liver disease in the appropriate broad diagnostic category. This then allows the
selection of further, more expensive and time-consuming inves- tigations such as ultrasound, CT
scanning, magnetic resonance spectroscopy, endoscopy and liver biopsy.
3 Following the progress of liver disease.
Hepatic anion transport: bilirubin

Measurement of bilirubin in blood and urine is usu- ally used to assess hepatic anion transport,
although other anions (such as bile salts) are also transported. Understanding the mechanisms by
which bilirubin is formed and removed is essential for the diagnosis of patients with jaundice
or liver disease, since abnor- mal levels of bilirubin in blood can occur in patients in whom
there is no liver disease.
Bilirubin production and metabolism
The pathway of bilirubin production and excretion is shown in Figure 13.2.
Production

The body usually produces about 300 mg of bilirubin per day as a breakdown product of haem. About
80% arises from red cells, with the remainder coming from red cell precursors destroyed in the bone
marrow (‘ineffective erythropoiesis’), and from other haem proteins such as myoglobin and the
cytochromes. Iron is removed from the haem molecule, and the porphyrin ring is opened to form
bilirubin.
Transport in plasma and hepatic uptake
Bilirubin is insoluble in water and is carried in plas- ma bound to albumin, and is thus not
filtered at the glomerulus unless there is glomerular proteinuria. On reaching the liver, the
bilirubin is taken into the hepatocyte by a specific carrier mechanism.

Conjugation of bilirubin and secretion into bile

In the endoplasmic reticulum of the hepatocyte, the enzyme bilirubin UDP-glucuronyltransferase
conju- gates bilirubin with glucuronic acid to produce biliru- bin glucuronides which are water
soluble and readily transported into bile. Secretion of bilirubin glucuro- nides into bile occurs
against a high concentration gradient and is the rate-limiting step in removing bili- rubin from
the body. Secretion is a carrier-mediated, energy-dependent process.

Further metabolism of bilirubin in the gut

Bilirubin glucuronides cannot be reabsorbed from the gut and are degraded by bacterial action,
mainly
in the colon, to a mixture of colourless, water-soluble
compounds collectively termed urobilinogen. These compounds oxidise to brown compounds known as
urobilins and stercobilins and are excreted in the fae- ces. A small percentage of urobilinogen is
absorbed and carried to the liver in the portal blood supply, that is, it undergoes an
enterohepatic circulation. Most of this urobilinogen is cleared by the liver, but a propor- tion
escapes clearance and is filtered at the kidney and appears in the urine, where it can be
detected using point of care urine dipsticks.


Measurements of serum bilirubin

Normally, more than 95% of bilirubin in serum is
unconjugated, but in liver disease the conjugated
form may predominate. For most purposes, the
measurement of serum [total bilirubin] (i.e. the sum of unconjugated and conjugated forms) is
sufficient, especially when results are interpreted in relation to the patient’s history,
findings on clinical examina- tion and the results of urine urobilinogen and biliru- bin
measurements. Occasionally, it may be helpful to measure serum [conjugated bilirubin] and serum
[unconjugated bilirubin] separately especially in
neonates (Chapter 21: Neonatal jaundice).