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بسم الله الرحمن الرحيم. Assessment of jaundice. By. Amr Abd Elmoty. Diagnostic approach. The diagnosis of jaundice is usually easy to establish based on history and observation of yellow discoloration of the sclerae , skin, and mucous membranes .
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Assessment of jaundice By AmrAbdElmoty
Diagnostic approach • The diagnosis of jaundice is usually easy to establish based on history and observation of yellow discoloration of the sclerae, skin, and mucous membranes. • It should be distinguished from pseudo-jaundice due to carotenaemia, in which the sclerae are spared
History • Risk factors leading to the development of jaundice should be sought, such as alcohol use, IV drug use, relevant occupational history, travel history to endemic regions, and sexual activity (number of partners; type of intercourse; known intercourse with hepatitis B virus-, hepatitis C virus-, or HIV-infected patients). • The CAGE score is highly specific for detecting alcohol abuse. It consists of 4 questions, and 2 positive answers require further investigation into alcoholism. These questions address efforts to cut down drinking, criticism about one's drinking, guilt, and need to drink upon waking in the morning
History • The possibility of pregnancy should be explored. The past medical history should include specific questioning identifying inflammatory bowel disease, pancreatic disorders, history of blood transfusions, anaemia, or the presence of an inherited haemoglobinopathy such as thalassaemia or sickle cell disease. Past surgical history should focus on procedures involving the hepatobiliary tract and the pancreas. • A review of prescription and OTC medication and herbal supplement use, both current and recent past, is recommended. Family history should inquire about symptoms of inherited anaemias, haemoglobinopathies, and liver disorders.
History • Of note, clinical manifestations range from completely asymptomatic to severely ill. The presenting symptoms tend to be non-specific, such as fatigue, malaise, pruritus, weight loss, anorexia, pale stool, and dark urine. Pain may occur but is not universal; it may suggest ascending cholangitis or a biliary stone.
Examination • The physical examination should focus on the liver and complications associated with cirrhosis. In general, a jaundiced patient with liver disease will be cachectic and ill-appearing. • In those with known or presumed liver disease, a careful skin examination may reveal track marks on the extremities, evidence of ecchymosis or petechiae, and, in some, the presence of spider angioma and palmarerythema. Muscle wasting is almost universal in patients with chronic liver disease. • Temporal wasting and loss of the thenar eminence may be observed.
Examination • The presence of parotid gland enlargement, gynaecomastia, and a Dupuytren's contracture is highly suggestive of chronic alcohol abuse. • The abdominal examination should include close inspection for collateral veins (caput medusa) and ascites. • The liver and spleen should be palpated and percussed during both inspiration and expiration, checking for enlargement, pain, and nodularity. • A nodular liver with decreased size suggests cirrhosis, and the presence of collateral vessels suggests portal hypertension.
Examination • Confusion or frank somnolence on continued questioning, asterixis, or altered deep tendon reflexes may be indicative of hepatic encephalopathy. • Lung examination may reveal evidence of pleural effusion (hepatic hydrothorax). • Cardiovascular examination may point towards liver dysfunction due to congestion from right heart failure. Rectal examination may reveal evidence of GI bleeding. • The presence or absence of a palpable gallbladder should be noted as well.
Examination • Courvoisier's law states that enlargement of the gallbladder with jaundice is likely to result from carcinoma of the head of the pancreas rather than a stone in the common duct. • With a common duct stone, the gallbladder is usually scarred from infection and does not distend.
Laboratory tests • Initial laboratory testing for all patients should include LFTs with fractionation of the bilirubin (direct and indirect), prothrombin time (PT) and INR, and FBC. • A low platelet count is suggestive of portal hypertension or alcohol abuse. Anaemia is a prominent feature in liver disease patients, prompting iron studies. • An increased PT and INR when coupled with a low albumin is indicative of synthetic liver dysfunction and suggestive of cirrhosis or acute liver failure.
Laboratory tests • In acute alcoholic hepatitis, application of the Glasgow Alcoholic Hepatitis Score is useful in the determination of the severity of disease and is of prognostic significance. • Maddrey’sDiscriminant Function index is a useful guide to rationalise the use of corticosteroids in severe disease: a score greater than 32 reflects severe disease. • Elevation can be seen in cholestasis without synthetic liver dysfunction, due to malabsorption of vitamin K. • Two patterns of liver function derangement have been described: cholestatic or hepatocellular.
Laboratory tests • The cholestatic pattern consists of predominant elevation of bilirubin, Alkphos, and gamma-GT, and the hepatocellular pattern consists of elevations of bilirubin, AST, and ALT. • These patterns are non-specific and can significantly overlap.
Laboratory tests • For specific cases additional tests are needed. • Autoimmune hepatitis should be excluded in all patients. Aminotransferase levels are usually more strikingly elevated than those of bilirubin and Alkphos. ESR, ANA, antismooth muscle antibody, anti-LKM-1 antibody, elevated gamma globulins, and anti-SLA antibody should be measured to exclude the diagnosis. Confirmatory diagnosis is with liver biopsy.
Laboratory tests • For specific cases additional tests are needed. • gG4 cholangiopathy diagnosis usually requires a combination of supporting clinical, laboratory, radiological, and histological data. Measured serum IgG4 ≥1.35 g/L (≥135 mg/dL) is 80% specific for the disease. Raised gamma-GT, Alkphos, and modest elevation of aminotransaminase levels support the diagnosis. Radiological appearances of simultaneous stricture of intra-pancreatic portion of the common bile duct and of the hepatic hilum with associated pancreatitis is more likely in IgG4 cholangiopathy.
Laboratory tests • For specific cases additional tests are needed. • Viral hepatitis: in patients with suspected exposure to or symptoms of hepatitis A, B, C, D, and E, the following laboratory tests are warranted: hepatitis A antibody IgM, hepatitis B serology or viral load, hepatitis C serology or viral load, and hepatitis D and E serologies/PCR. • Haemolysis or haemolyticanaemia: in patients with pallor, weakness, shortness of breath, or dark-coloured urine, tests should include haptoglobin, LDH, a reticulocyte count, and a peripheral blood smear. If a transfusion reaction is suspected, a direct antiglobulin test is also indicated. Some patients may need work-up for sickle cell anaemia.
Laboratory tests • For specific cases additional tests are needed. • Haemochromatosis: patients suspected of haemochromatosis should receive a transferrin saturation test, iron studies, a genetic test to determine the HFE mutation (confirmatory), and a liver biopsy. These patients tend to have joint pain, fatigue, lack of energy, abdominal pain, and cardiac problems. • Primary biliary cirrhosis: this may be the cause of jaundice in patients with fatty subcutaneous deposits, fluid retention, and dry eyes and mouth. Tests should include a liver biopsy and a blood test to identify the antimitochondrial antibody.
Laboratory tests • For specific cases additional tests are needed. • Alpha-1 antitrypsin deficiency: serum level and genotype looking for the Z or M (Malton) alleles are warranted with a suspicious family history (liver or lung disease in those younger than 40 years of age) and symptoms of alpha-1 antitrypsin deficiency (e.g., emphysema), and when other diagnoses are ruled out. • Wilson's disease: a genetic test is indicated if signs and symptoms are suspicious (tremor, Kayser-Fleischer rings, ascites, hepatitis by 20s), and other diagnoses have been ruled out. A liver biopsy with copper concentration, serum ceruloplasmin, and urinary copper excretion measurements is needed.
Laboratory tests • For specific cases additional tests are needed. • Crigler-Najjar syndrome (type 1 or 2): if suspected, a further work-up is recommended. Patients may have a family history of Crigler-Najjar and worsening jaundice of the skin and sclerae with an onset on the second or third day of life and persisting beyond 2 weeks. Unconjugated and total bilirubin levels tend to be elevated, whereas conjugated bilirubin would be low. A liver biopsy or enzyme assay should be completed to look for low or absent glucuronyltransferase. The phenobarbital test can be used to distinguish type 1 and type 2. In type 1, there is no resulting change in bilirubin, and in type 2, bilirubin levels are decreased. Finally, a chromatographic analysis of bile helps distinguish type 1 and type 2.
Laboratory tests • For specific cases additional tests are needed. • Parasitic disease: patients with recent foreign travel to endemic regions may have parasitic disease causing jaundice. A stool study, analysing ova and parasites, is needed. Ultrasound and cholangiography are also helpful in identifying parasites. • AIDS cholangiopathy: the diagnosis is one of exclusion in a patient with known HIV infection. The cholangiopathy may be related to highly active antiretroviral therapy (HAART), HIV itself, or comorbid and opportunistic infections. ERCP can provide therapy in the form of biliarysphincterotomy, dilation, and/or stenting of the biliary strictures.
Estimating the pre-test probability of biliary obstruction • Once the initial clinical assessment and laboratory tests are complete, the pre-test probability of biliary obstruction should be estimated in order to guide the choice of imaging. • Most patients require some form of imaging so that mechanical obstruction can be definitively excluded and clues to hepatic and post-hepatic causes identified. • The ACR appropriateness criteria for jaundice define the following major categories:
Estimating the pre-test probability of biliary obstruction • High likelihood of benign biliary obstruction: patients present with jaundice and acute abdominal pain. • High likelihood of malignant biliary obstruction: patients typically present with insidious development of jaundice and associated constitutional symptoms (weight loss, fatigue, etc.) • Low likelihood of mechanical obstruction: history, clinical features, and initial laboratory tests consistent with specific hepatic and post-hepatic causes (e.g., history of alcohol use or exposure to infectious agent, painless jaundice without constitutional symptoms, hepatocellular pattern of LFTs) • Indeterminate likelihood of obstruction: confusing clinical presentation.
High likelihood of benign biliary obstruction • Ultrasound is the preferred initial modality of investigation, as it is accurate, inexpensive, readily available, and non-invasive (sensitivity of 55% to 95% and specificity of 71% to 96%). • It is limited by its decreased sensitivity for detecting biliaryductal calculi and the inability to visualise the distal common bile duct if obscured by overlying bowel gas. • In patients with acute biliary obstruction and suspected complicating conditions such as cholangitis, cholecystitis, or pancreatitis not well evaluated by sonography, a pre-intravenous and post-intravenous contrast-enhanced abdominal CT study is useful in defining the level of obstruction, likely cause, and co-existent complications.
High likelihood of benign biliary obstruction • CT can detect partially calcified biliary calculi but is relatively insensitive for detecting bilirubinate or cholesterol calculi. • If patients have suspected sclerosingcholangitis or biliary stricture, MRCP is useful to assist in delineating the biliary tree and guiding the need for endoscopic retrograde cholangiopancreatography (ERCP) or percutaneoustranshepaticcholangiography (PTC) to achieve drainage. • This approach decreases the risk of development of a suppurativecholangitis, which may occur with a failed ERCP in a dilated biliary system.
High likelihood of malignant biliary obstruction • Ultrasound is used to confirm the presence of biliary obstruction, but patients require further imaging to confirm the diagnosis. • Malignant obstruction is most commonly due to pancreatic carcinoma but may be secondary to cholangiocarcinoma of either the proximal or distal duct or to periductal nodal compression. • A contrast-enhanced multipass CT examination with multi-planar reformation has high sensitivity for lesion detection and 70% accuracy in discriminating resectable and unresectable disease.
High likelihood of malignant biliary obstruction • It has a sensitivity of 74% to 96% and specificity of 90% to 94% for detecting biliary obstruction. Important information in tumour staging includes tumour contiguity or invasion of the superior mesenteric and portal veins, peri-pancreatic tumour extension, regional adenopathy, and hepatic metastases. • In cases where CT and sonography are equivocal, ERCP and endoscopic ultrasound may provide imaging and allow a cytological diagnosis to be made using fine needle aspiration.
Low likelihood of mechanical obstruction • Ultrasound is the preferred imaging modality to exclude mechanical obstruction. MRCP may also be considered. • In patients with decompensated chronic liver disease with jaundice and ascites, the addition of portal tract Doppler studies at the time of ultrasonography and subsequent triphasic CT imaging of the liver would be useful to exclude portal vein occlusion.
Indeterminate likelihood of obstruction • The imaging work-up is frequently geared to the dominant clinical symptom. • Ultrasound is certainly appropriate if the sole question is whether obstruction exists. • In cases in which most of the abdominal organs need to be assessed, either CT or MRI can be used, although CT more reliably displays all abdominal anatomy.
Thank you
