Jaundice

Published on 02/03/2015 by admin

Filed under Basic Science

Last modified 22/04/2025

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Jaundice

Jaundice is a yellow discoloration of the skin or sclera (Fig 29.1). This is due to the presence of bilirubin in the plasma and is not usually detectable until the concentration is greater than about 50 µmol/L. Normally the bilirubin concentration in plasma is less than 21 µmol/L.

Fig 29.1 Jaundice in the sclera of an eye.

Bilirubin is derived from the tetrapyrrole prosthetic group found in haemoglobin and the cytochromes. It is normally conjugated with glucuronic acid to make it more soluble, and excreted in the bile (Fig 29.2). There are three main reasons why bilirubin levels in the blood may rise (Fig 29.3).

Fig 29.2 Bilirubin metabolism.

Fig 29.3 Causes of jaundice.

Haemolysis. The increased haemoglobin breakdown produces bilirubin, which overloads the conjugating mechanism.

Failure of the conjugating mechanism within the hepatocyte.

Obstruction in the biliary sytem.

Both conjugated bilirubin and unconjugated bilirubin may be present in plasma. Conjugated bilirubin is water-soluble. Unconjugated bilirubin is not water-soluble and binds to albumin from which it may be transferred to other proteins such as those in cell membranes. It is neurotoxic, and if levels rise too high in neonates, permanent brain damage can occur.

Biochemical tests

Bilirubin metabolites are responsible for the brown coloration of faeces. If bilirubin does not reach the gut, stools become pale in colour. Bilirubin in the gut is metabolized by bacteria to produce stercobilinogen. This is partly reabsorbed and re-excreted in the urine as urobilinogen, and may be detected by simple biochemical tests. When high levels of conjugated bilirubin are being excreted, urine may be a deep orange colour, particularly if allowed to stand.

This combination of pale stools and dark urine is characteristic of extrahepatic obstruction of the biliary tract. This is often amenable to surgery, hence the term ‘surgical jaundice’.

Differential diagnosis

Jaundice may be a consequence of haemolysis, cholestasis or hepatocellular damage. The causes and features of these are summarized in Figure 29.3 and Table 29.1. In addition there are inherited disorders of bilirubin metabolism. Gilbert’s disease is the most common and causes a mild unconjugated hyperbilirubinaemia because of defective hepatic uptake of bilirubin. In this condition bilirubin levels rise on fasting.

Table 29.1

Laboratory differential diagnosis of jaundice

Haemolysis

Increased bilirubin production caused by haemolysis gives a predominantly unconjugated hyperbilirubinaemia. This, in combination with immature liver function, is commonly encountered in babies. A rapidly rising bilirubin in a neonate should be carefully monitored as it may give rise to brain damage (kernicterus). If the concentration approaches 200 µmol/L, phototherapy should be used to break down the molecule in the skin and reduce the level. If the concentration rises above 300 µmol/L, exchange transfusion may be necessary.

Extrahepatic biliary obstruction

Gallstones can partially or fully block the bile duct. Such a blockage is known as extrahepatic obstruction. If the blockage is complete, both bilirubin and alkaline phosphatase are raised. There is little or no urobilinogen in urine. Stools will be pale in colour. When the obstruction is removed, the stools regain their colour and urine again becomes positive for urobilinogen. If the blockage is only partial, alkaline phosphatase may be high, although serum bilirubin may well be within the reference interval. This is a classic picture of an isolated secondary neoplasm in the liver, partly disturbing the biliary tree. The normal functioning part of the liver is sufficient to process and excrete the bilirubin. The levels of alkaline phosphatase released into serum will mirror the degree of obstruction. Intrahepatic biliary obstruction is much more difficult to diagnose than extrahepatic obstruction. The bile canaliculi can become blocked due to cirrhosis, liver cancer or infection. This leads to an increased concentration of conjugated bilirubin in serum.

Case history 23

A 65-year-old man came to his GP’s surgery with visible jaundice that he had noticed to be deepening in colour. He had no pain but had noticed some weight loss and that his stools were pale. He was a moderate drinker, and was not on any drug therapy. His LFTs were:

• What is the differential diagnosis?

• What other investigations would be helpful in making a diagnosis?

Comment on page 166.

Clinical note

CT scanning is an invaluable tool in the investigation of the jaundiced patient. The dilated bile ducts (arrow) are clearly visible in a CT scan of a patient with extrahepatic obstructive jaundice due to carcinoma of the head of the pancreas (Fig 29.4).

Fig 29.4 CT scan of liver and gall bladder.

Hepatocellular damage

Obstruction may be secondary to damage to the hepatocytes by infection or toxins, rather than damage to the biliary tract. The most common causes of acute jaundice seen in adults are viral hepatitis and paracetamol poisoning. In these cases, not only are the bilirubin and alkaline phosphatase levels raised, but AST and ALT are elevated indicating hepatocellular damage.

Jaundice

Jaundice indicates that there is an elevated concentration of bilirubin in plasma.

In neonates it is important to determine the concentration of total and conjugated bilirubin to aid diagnosis and decide on treatment.

In adults, the most common cause of jaundice is obstruction, and this is confirmed by the elevation of both bilirubin and alkaline phosphatase.

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