Jaundice (icterus) is detectable when the serum bilirubin is greater than 30-60 /-Lmollitre-I (3 mg dl'”). The usual division of jaundice into prehepatic, hepatocellular and obstructive (cholestatic) is an oversimplification as in hepatocellular jaundice there is invariably cholestasis and the clinical problem is whether the cholestasis is intrahepatic or extrahepatic. Jaundice will therefore be considered under the following headings:
HAEMOLYTIC JAUNDICE-increased bilirubin load for the liver cells
CONGENITAL HYPERBILIRUBINAEMIAs-defects in conjugation.
CHOLESTATIC JAUNDICE, including hepatocellular (parenchymal) liver disease and large duct obstruction.
The increased breakdown of red cells leads to an increase in production of bilirubin. The resulting jaundice is usually mild (serum bilirubin of 68-102 /-Lmol litre-I [4-6 mg dl-I]) as normal liver function can easily handle the increased bilirubin derived from excess haemolysis. Unconjugated bilirubin is not water soluble and therefore will not pass into the urine, hence the term ‘acholuric jaundice’. Urinary urobilinogen is increased. The causes of haemolytic jaundice are those of haernolytic anaemia . The clinical features depend on the cause; anaemia, jaundice, splenomegaly, gallstones and leg ulcers may be seen.
Investigations show features of haemolysis .
The level of unconjugated bilirubin is raised but the serum AP, transferases and albumin are normal. Serum haptoglobulins are low.
The differential diagnosis is from other forms of jaundice.
GILBERT’S SYNDROME. This is the commonest familial hyperbilirubinaemia and affects 2-5% of the population.
It is asymptomatic and is usually detected as an incidental finding of a slightly raised bilirubin (3-5 mg dl-I; 51- 85/-Lmol litre-I) on a routine check. No signs of liver disease are seen. There is a family history of jaundice in 5-15% of patients. The aetiology of the syndrome is multifactorial and many abnormalities of bilirubin handling have been demonstrated. It is possible that this condition merely represents one end of the normal distribution curve.
The major importance of establishing this diagnosis is to inform the patient that this is not a serious disease and to prevent unnecessary investigation in the future. Investigations show only a raised unconjugated bilirubin, which rises on fasting and during a mild illness. The reticulocyte count is normal. No treatment is necessary.
CRIGLER-NAJJAR SYNDROME. This is very rare. Only type II (autosomal dominant) with a decrease rather than absence (Type I-autosomal recessive) of glucuronyl transferase can survive into adult life. Liver histology is normal. Transplantation is the only effective treatment.
In the Dubin-Iohnson (autosomal recessive) and Rotor (possibly autosomal dominant) syndromes, there are defects in bilirubin handling in the liver. The prognosis is good in both. In the former the liver is black due to melanin deposition.
This can be divided into:
INTRAHEPATIC CHOLESTASIS, due to the swelling of bhepatocytes and oedema in parenchymal liver damage (hepatocellular) or to an excretory dysfunction of the bile canaliculi at a cellular level
EXTRAHEPATIC CHOLESTASIS, due to large duct obstruction of bile flow at any point in the biliary tract distal to the bile canaliculi.
Clinically there is jaundice with pale stools and dark urine in both types and the serum bilirubin is conjugated. Intrahepatic and extrahepatic cholestatic jaundice must be differentiated, as their clinical management is entirely different.
The differential diagnosis of jaundice
A careful history may give a clue to the diagnosis. Patients should be asked a series of questions, keeping in mind that certain causes of jaundice are more likely in particular categories of people. A young person is more likely to have hepatitis and therefore questions about drug and alcohol abuse and homosexuality should be asked. An elderly person with gross weight loss is more likely to have a carcinoma. All patients may complain of malaise. Abdominal pain occurs in patients with biliary obstruction due to gallstones and, sometimes with an enlarged liver, there is pain due to distension of the capsule. Questions should be appropriate to the particular situation and the following aspects of the history should be covered.
COUNTRY OF ORIGIN-the incidence of hepatitis B virus (HBV) infection is increased in Africa and the Far East.
DURATION OF ILLNEss-a history of jaundice with prolonged weight loss in an older patient suggests malignancy; a short history, particularly with a prodromal illness of malaise, suggests a hepatitis
RECENT OUTBREAK of jaundice in the communitysuggests hepatitis A virus (HA V)
RECENT CONSUMPTION of shellfish-suggests HAV
INTRAVENOUS DRUG ABUSE, RECENT INJECTIONS OR TATTOOS-all increase chance of HBV and hepatitis C virus (ncv) infection
MALE HOMOSEXUALITy-increases chance of HBV infection
FEMALE PROSTITUTION-increased HBV infection
BLOOD TRANSFUSIONS or infusion of pooled blood products-in developed countries all are screened for HBV and HeV
ALCOHOL CONSUMPTION-a careful history of drinking habits is taken, although many patients often lie about the actual amount they drink
DR UGS TAKEN, particularly in the previous 2-3 months-many drugs cause jaundice.
TRAVEL to areas with increased risk of HAV infection RECENT ANAESTHETICS, e.g. halothane may cause jaundice
FAMILY HISTORy-patients with, for example, Gilbert’s disease may have family members who get recurrent jaundice
RECENT SURGERY on the biliary tract or for carcinoma
PEOPLE ENGAGED IN RECREATIONAL ACTIVITIES in rural areas as well as farm and sewage workers are at risk for leptospirosis.
FEVERS OR RIGORS-suggestive of cholangitis or possibly a liver abscess
The signs of acute and chronic liver disease should be looked for (see p. 246). Certain additional signs may be useful:
HEPATOMEGALy-a smooth tender liver is seen in hepatitis and with extrahepatic obstruction, but a knobbly irregular liver suggests metastases. Causes of hepatomegaly are shown.
SPLENOMEGALy indicates portal hypertension in patients when signs of chronic liver disease are present. The spleen can also be ‘tipped’ occasionally in viral hepatitis.
ASCITES is found in cirrhosis but can also be due to carcinoma (particularly ovarian) and many other causes.
A PALPABLE GALLBLADDER can suggest a carcinoma of the pancreas obstructing the bile duct.
GENERALIZED LYMPHADENOPATHY suggests a lymphoma.