CME General Internal Medicine for the Physician – II Acute jaundice Liver function and the results of other weight gain, but in severe forms oedema standard liver tests are otherwise normal and ascites may be present. Bruising may in all three conditions. be spontaneous or at sites of venepunc- ture. Serum biochemistry shows increase Andrew Burroughs FRCP in transaminases, while serum albumin Lucy Dagher MD Liver disease levels may be low and prothrombin time Liver Transplantation & Hepatobiliary Generalised impairment of hepato- prolonged. Medicine, Royal Free Hospital, London cellular function may result from acute liver injury or chronic disease. A variety Obstruction of the bile ducts Clin Med JRCPL 2001;1:285–9 of disorders can produce acute or subacute hepatocellular injury The bile ducts may be obstructed including: because of mechanical obstruction of the The normal serum bilirubin concentra- viral hepatitis biliary tree by the presence of stones or tion in adults is less than 18 mmol/l. exposure to hepatotoxins by intrinsic disorders of the bile duct and Jaundice is best looked for in the sclerae extrinsic compression, most commonly hepatic ischaemia and mucous membrane of the soft palate cholangiocarcinoma and carcinoma of and is a common sign in almost all liver certain metabolic derangements. the pancreas, respectively. Without and biliary tract diseases. There are sev- Jaundice appears over days or weeks. mechanical obstruction the most eral important questions of value in Fatigue and malaise are common. There common causes of cholestatic jaundice determining the diagnosis which the may be varying degrees of decompensa- are drug induced and following hepatitis clinician should ask himself/herself: tion due to cirrhosis or just cutaneous A. The patient does not have signs of 1Is the jaundice due to an markers of chronic liver disease. Signs of chronic liver disease but may have signs obstruction of the biliary tree? hepatic encephalopathy, if present, may indicating malignancy. Pruritus is usual, 2Is there evidence of chronic liver be personality change, and in more and the patient becomes increasingly disease? severe cases manifest as flapping tremor, pigmented. There are raised levels of confusion and coma. Fluid retention in conjugated bilirubin, biliary alkaline 3Is the jaundice possibly drug its mildest form may be exhibited as phosphatase and total cholesterol in the induced, alcohol induced or infective in origin? 4Is there any evidence of haemolysis? Fig 1. Classification of jaundice. Classification of jaundice (Fig 1) JAUNDICE Jaundice can result from either an increase in bilirubin formation or a decrease in hepatic clearance. From a Hepatocellular practical standpoint, it is reasonable to Isolated bilirubin Cholestatic classify conditions that produce jaundice transport defects haemolysis under three broader categories: Acute Chronic 1Isolated disorders of bilirubin Dilated ducts Undilated ducts metabolism. 2Liver disease. 3Obstruction of the bile ducts. Table 1. Disorders of bilirubin metabolism. Unconjugated hyperbilirubinaemia: Isolated disorders of bilirubin Increased bilirubin production Haemolysis metabolism (Table 1) Ineffective erythropoiesis The mechanisms that can lead toisolated Blood transfusion Resorption of haematomas unconjugated hyperbilirubinaemia are: Decreased hepatocellular uptake Drugs (eg rifampicin) increased bilirubin production Gilbert syndrome decreased hepatocellular uptake Decreased conjugation Gilbert syndrome decreased bilirubin conjugation. Crigler-Najar syndrome Physiologic jaundice of the newborn Hyperbilirubinaemia is often associ- Conjugated or mixed hyperbilirubinaemiaD ubin-Johnson syndrome ated with a predominant elevation in Rotor syndrome indirect serum bilirubin concentration. Clinical Medicine Vol 1No 4 July/August 2001 285 CME General Internal Medicine for the Physician – II Key Points some can cause haemolysis. Drug inges- tion may need to be sought by searching Scleral jaundice can be detected if serum bilirubin is above 34 mmol/l, but more the patient’s home and workplace and by commonly 50 mmol/l is the threshold re-taking the history as well as checking general practitioner (GP) records. A careful history, physical examination and review of the standard laboratory tests Ingestion of significant quantities of should allow a physician to make an accurate diagnosis in 85% of cases paracetamol or the mushroom Amanita In acute jaundice, liver ultrasound should be the first imaging modality phalloides may lead to hepatocellular necrosis and jaundice within several days If there is evidence of biliary obstruction and a therapeutic intervention is planned, of exposure 2. Toxic liver injury can have a endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography is the investigation of choice fulminant course associated with a high mortality. Several drugs can produce Magnetic resonance cholangiopancreatography should follow ultrasound if the idiosyncratic hepatocellular injury and latter has been technically difficult, if obstruction has not been ruled out or jaundice, the most common being non- therapeutic intervention is not needed steroidal anti-inflammatory drugs Liver biopsy is needed to confirm the presence, cause and severity of chronic liver (NSAIDs), amiodarone, terbinafine, iso- disease niazid, methyldopa, phenytoin and the inhalational anaesthetic halothane. Excessive alcohol intake is especially serum. Steatorrhoea is responsible for increased exposure not only to viral important because it is common; a weight loss and malabsorption of cal- hepatitis but also to a greater number of detailed history of alcohol consumption cium and fat-soluble vitamins A, D, E rarer causes of jaundice such as malaria, should be taken from the patient, rela- and K. and inherited haemoglobinopathies. A tives and the GP. Alcoholic hepatitis In adult patients with new onset of family history is important with regard should be a diagnostic consideration in jaundice, eight disorders account for to heritable disorders of bilirubin metab- the jaundiced patient with ethanol 98% of the diagnoses ultimately olism such as Gilbert syndrome, chronic dependency, particularly when hepato- established 1: liver disease such as Wilson’s disease, megaly and fever are present. viral hepatitis haemochromatosis and autoimmune Physical examination alcoholic liver disease conditions which may be associated with chronic active hepatitis or PBC. Special chronic hepatitis Signs and symptoms attention should be paid to identifying drug induced liver diseases groups at particular risk of contracting A history of fever, especially accom- gallstones and their complications infective viral hepatitis such as intra- panied by shaking chills, or abdominal carcinoma of the pancreas venous (IV) drug abusers, homosexuals, pain particularly in the right upper primary biliary cirrhosis (PBC) following needle-stick injuries or contact quadrant, is suggestive of cholangitis primary sclerosing cholangitis. with jaundiced individuals, and patients caused by obstructive diseases (particu- who have received blood transfusions. larly choledocholithiasis), as is a history By the time patients with metastatic Drugs and environmental hepato- of biliary surgery. Symptoms compatible liver disease develop jaundice, the diag- toxins may not only be hepatotoxic but with viral prodrome, such as anorexia, nosis is usually obvious because the liver has been extensively replaced by tumour tissue. Fig 2. History taking in acute jaundice. Careful history, physical examination Raw fish and review of standard laboratory tests Transfusion and Newborns of should allow a physician to make an transplant recipients long-term carriers accurate diagnosis in 85% of cases 1. Alcohol Multiple Family history sexual partners History History (Fig 2) Intravenous Prescription taking drug users An accurate clinical history is medication in acute Over-the-counter jaundice particularly important in differentiating drugs Prisoners the various causes of jaundice. In con- Vitamins Institutionalised junction with examination, it determines Herbal remedies people the most appropriate investigations. Healthcare Body-piercing, The increase in foreign travel and workers Hepatoxins tattoos migration to developed countries have 286 Clinical Medicine Vol 1No 4 July/August 2001 CME General Internal Medicine for the Physician – II Table 2. Signs and symptoms of viral hepatitis. aspartate aminotransferase to alanine aminotransferase appears to be a useful Infection index for distinguishing non-alcoholic Short-term Long-term steatohepatitis (NASH) from alcoholic (acute) (chronic) liver disease. Although ratios less than 1 suggest NASH or viral hepatitis, a ratio Tiredness, anorexia, malaise, myalgias Same symptoms as acute of 2 or above strongly suggests alcoholic Nausea or stomach ache Muscle and joint ache liver disease 3,4. Gamma-glutamyl trans- Diarrhoea Weakness Skin rash Signs & symptoms of cirrhosis ferase elevation strengthens the diagnosis Yellow eyes/skin (jaundice) Signs & symptoms of liver cancer of alcohol abuse. A drug effect is possible Light-coloured stools Secondary amenorrhoea if there is a correlation between the onset Dark yellow urine of jaundice, elevation of liver enzymes and the start of drug administration. The drugs that most commonly cause malaise and myalgias point to viral which the liver is usually enlarged. The transaminase abnormalities are NSAIDs, hepatitis (Table 2). Systemic features