Clinical Review ABC of diseases of liver, pancreas, and biliary system

Investigation of liver and biliary disease

BMJ 2001; 322 doi: http://dx.doi.org/10.1136/bmj.322.7277.33 (Published 06 January 2001) Cite this as: BMJ 2001;322:33

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  1. I J Beckingham,
  2. S D Ryder

    Jaundice is the commonest presentation of patients with liver and biliary disease. The cause can be established in most cases by simple non-invasive tests, but many patients will require referral to a specialist for management. Patients with high concentrations of bilirubin (>100 μmol/l) or with evidence of sepsis or cholangitis are at high risk of developing complications and should be referred as an emergency because delays in treatment adversely affect prognosis.

    Bilirubin pathway

    Jaundice

    Hyperbilirubinaemia is defined as a bilirubin concentration above the normal laboratory upper limit of 19 μmol/l. Jaundice occurs when bilirubin becomes visible within the sclera, skin, and mucous membranes, at a blood concentration of around 40 μmol/l. Jaundice can be categorised as prehepatic, hepatic, or posthepatic, and this provides a useful framework for identifying the underlying cause.

    Around 3% of the UK population have hyperbilirubinaemia (up to 100 μmol/l) caused by excess unconjugated bilirubin, a condition known as Gilbert's syndrome. These patients have mild impairment of conjugation within the hepatocytes. The condition usually becomes apparent only during a transient rise in bilirubin concentration (precipitated by fasting or illness) that results in frank jaundice. Investigations show an isolated unconjugated hyperbilirubinaemia with normal liver enzyme activities and reticulocyte concentrations. The syndrome is often familial and does not require treatment.

    Prehepatic jaundice

    In prehepatic jaundice, excess unconjugated bilirubin is produced faster than the liver is able to conjugate it for excretion. The liver can excrete six times the normal daily load before bilirubin concentrations in the plasma rise. Unconjugated bilirubin is insoluble and is not excreted in the urine. It is most commonly due to increased haemolysis—for example, in spherocytosis, homozygous sickle cell disease, or thalassaemia major—and patients are often anaemic with splenomegaly. The cause can usually be determined by further haematological tests (red cell film for reticulocytes and abnormal red cell …

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