Jaundice (icterus) is a yellow discoloration of the sclerae and skin as a result of a raised serum bilirubin. It is usually detectable clinically when the bilirubin exceeds 50 |imol/L (3 mg/dL).
Bilirubin is derived predominantly from the breakdown of haemoglobin in the spleen, and is carried in the blood bound to albumin. Unconjugated bilirubin is conjugated in the liver by glucuronyl transferase to bilirubin glu-curonide, and this is excreted via the bile duct into the small intestine in bile. In the terminal ileum conjugated bilirubin is converted to urobilinogen and excreted in the faeces (as stercobilinogen, responsible for the pigmentation of faeces) or reabsorbed and excreted by the kidneys (Fig. 4.2).
For clinical and diagnostic purposes three major categories of jaundice can be considered:
■ Haemolytic jaundice
■ Congenital hyperbilirubinaemias - impaired conjugation of bilirubin or bilirubin handling by the liver. Liver biochemistry is normal other than raised bilirubin.
■ Cholestatic jaundice - failure of bile secretion by the liver or bile duct obstruction. Liver biochemistry is abnormal.
Increased breakdown of red blood cells leads to increased production of bilirubin, which usually results in mild jaundice only (68-102 |imol/L or 4 -6 mg/dL), as the liver can usually handle the increased bilirubin derived from haemolysis. The unconjugated bilirubin is not water soluble and there-fore does not pass into the urine, unlike the conjugated hyperbilirubinaemia of cholestatic jaundice. Urinary urobilinogen is increased. The causes are those of haemolytic anaemia (p. 206), with the clinical features dependent on the cause. Investigations show features of haemolysis (p. 207), with raised serum unconjugated bilirubin and otherwise normal liver biochemistry.
The most common congenital hyperbilirubinaemia is Gilbert's syndrome, which affects 2-7% of the population. It is asymptomatic and is usually picked up as an incidental finding of a slightly raised serum bilirubin (17102 |imol/L, 1-6 mg/dL). Mutations in the gene coding for UDP-glucuronyl transferase lead to reduced enzyme activity and reduced conjugation of
Fig. 4.2 Pathways in bilirubin metabolism.
bilirubin with glucuronic acid. Diagnosis is based on the findings of uncon-jugated hyperbilirubinaemia with otherwise normal liver biochemistry, normal full blood count, smear and reticulocyte count (thus excluding haemolysis) and absence of signs of liver disease. The patient should be reassured that no further investigation or treatment is necessary.
Other congenital abnormalities of bilirubin metabolism (Crigler-Najjar, Dubin-Johnson and Rotor's syndromes, benign recurrent intrahepatic cholestasis) are rare.
This can be divided into the following (Fig. 4.3):
■ Intrahepatic cholestasis, caused by hepatocellular swelling in parenchy-mal liver disease or abnormalities at a cellular level of bile excretion
■ Extrahepatic cholestasis resulting from obstruction of bile flow at any point distal to the bile canaliculi.
In both types there is jaundice with pale stools and dark urine and the bilirubin is conjugated.
Fig. 4.3 Causes of jaundice.
However, intrahepatic and extrahepatic choleslatic jaundice must be dif-ferentiated as their management is quite different.
An outline of the approach to the investigation of jaundice is shown in Fig. 4.4.
■ Serum liver biochemistry will confirm the jaundice. The AST tends to be high early in the course of hepatitis, with a smaller rise in alkaline phos-phatase. Conversely, in extrahepatic obstruction the alkaline phosphatase is elevated, with a smaller rise in the AST.
■ US examination shows dilated bile ducts in extrahepatic cholestasis and may identify the level of obstruction and the cause e.g. gallstones, tumours.
■ Serum viral markers for hepatitis A or hepatitis B are present in acute viral hepatitis. Antibodies to hepatitis C virus develop late in the course of acute infection but HCV RNA is usually detectable by 1-2 weeks.
■ Other tests - prothrombin time may be prolonged as a result of vitamin K malabsorption and is corrected by administration of vitamin K (p. 242). Serum autoantibodies are present in autoimmune liver disease (see later).
ERCP = endoscopic retrograde cholangiopancreatography
MRCP = magnetic resonance cholangiopancreatography
PTC = percutaneous transhepatic cholangiogram
Fig. 4.4 Approach to the investigation of cholestatic jaundice. The order of investigation is influenced by the age of the patient and hence the likely cause of jaundice. A young person is most likely to have intrinsic liver disease, e.g. viral hepatitis, and it may be more appropriate to organize tests to exclude these conditions before proceeding to US. See page 150 for clinical features.
1. Ethics and communication
2. Infectious diseases
3. Gastroenterology and nutrition
4. Liver, biliary tract and pancreatic disease
Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
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LIVER DISEASE IN PREGNANCY
CARCINOMA OF THE PANCREAS
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THE SERONEGATIVE SPONDYLOARTHROPATHIES
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