Evaluation of a patient with Jaundice

1. Evaluation of a patient with Jaundice Dr Yousif. A Qari Assist prof. consultant gastroenterologist KAUH, Jeddah, Saudi Arabia

2. Definition of Jaundice • Jaundice, as in the French jaune, refers to the yellow discoloration of the skin. • It arises from the abnormal accumulation of bilirubin in body tissues, which occurs when the serum bilirubin level exceeds 3 mg/dL or 50 mmol/L.

3. Laboratory Tests Total and direct bilirubin assays . Conjugated hyperbilirubinemia Unconjugated hyperbilirubinemia

4. Hemolysis Glucose-6-phosphate deficiency Pyruvate kinase deficiency Drugs Ineffective erythropoiesis Neonatal causes Physiologic abnormalities Lucy-Driscoll syndrome Breast milk Uridine diphosphate glucuronosyltransferase deficiencies Gilbert syndrome Crigler-Najjar syndromes (I and II) Miscellaneous causes Drugs Hypothyroidism Thyrotoxicosis Pulmonary infarct Fasting Causes Of HyperbilirubinemiaUNCONJUGATED FORM

5. Congenital causes Rotor syndrome Dubin-Johnson syndrome Choledochal cysts Familial disorders Benign recurrent intrahepatic cholestasis Cholestasis of pregnancy Hepatocellular defects Alcohol abuse Viral infection Sepsis Cholestatic Primary biliary cirrhosis Primary sclerosing cholangitis Biliary obstruction Pancreatic disease Systemic disease Infiltrative disorders Postoperative complications Renal disease Drugs Causes Of HyperbilirubinemiaCONJUGATED FORM

6. Several questions must be answered initially 1. Is the elevated bilirubin conjugated or unconjugated? 2. If the hyperbilirubinemia is unconjugated, is it caused by • increased production • decreased uptake • impaired conjugation 3. If the hyperbilirubinemia is conjugated, is the problem • intrahepatic or • extrahepatic? 4. Is the process acute or chronic?

7. Conjugated hyperbilirubinemia • Usually acquired disease • Intrahepatic or Extrahepatic (obstructive) cause. • Acute disease usually can be differentiated from chronic disease by the patient's history, physical examination, and laboratory tests • clinical evaluation • xanthelasma, • spider angioma, • ascites, • hepatosplenomegaly. • Laboratory evidence of chronic disease • Hypoalbuminemia, • Thrombocytopenia, • uncorrectable prolongation of the prothrombin time.

8. Cholestasis • Chronic cholestasis may arise from • Cirrhosis, • Primary sclerosing cholangitis, • Primary biliary cirrhosis, • Secondary biliary cirrhosis, • Carcinoma • Drugs. • Acute disease. • New-onset bilirubinuria • Fever • Right upper quadrant pain, • Tenderness, • Hepatomegaly,

9. Investigation of a patient with jaundice • History of presentation • Medication use • Past medical history • Physical examination • Evaluation of liver function tests

10. First evaluating a patient with hyperbilirubinemia Quick assessment of the emergency of the situation • Fever, • Leukocytosis • Hypotension • Asterixis • Confusion • Stupor severe hepatocellular dysfunction fulminant hepatocellular failure Ascending cholangitis Immediate therapy

11. History • Family history of liver disease • Alcohol and drug history • Sexual history • Transfusion history • Nutrition history • Exposure to • Environmental toxins • Persons with jaundice • Drugs (e.g., prescription, nonprescription, intravenous) • , • Outbreaks or epidemics in the community • Previous liver function tests are valuable • History of biliary or pancreatic disease.

12. History • Shaking chills or fevers point toward cholangitis or bacterial infection • Abdominal pain may indicate pancreatic disease, especially if it radiates to the back • Right upper quadrant ache point toward Viral hepatitis • Weight loss, anorexia, nausea, and vomiting are not helpful signs because most patients with hepatobiliary disease or obstruction have anorexia and some weight • Pruritus can be associated with both intrahepatic cholestasis as well as biliary obstruction.

13. History Age: • < 30 years ——›acute parenchymal disease • > 65 years ——› stones or malignancies • 30 - 50 years ——› chronic liver disease • Children and young adults ——› viral hepatitis

14. History Sex: • Men are more likely to develop • Cirrhosis secondary to alcohol • Pancreatic cancer • Hepatocellular carcinoma, • Hemochromatosis • Women are more likely to have • Primary biliary cirrhosis • Gallstones • Chronic active hepatitis

15. Physical Examination • Examination of the liver • Examination of spleen • Examination for evidence of stigmata of chronic liver disease • Palmar erythema • Dupuytren contracture • Abnormal nails • Parotid enlargement • Xanthelasmas • Gynecomastia • Spider nevi • Dilated veins. • Jaundice must be differentiated from • Hypercarotenemia • Uremic pigmentation • Picric acid ingestion • Quinacrine therapy

16. Physical Examination • Shrunken, nodular liver may ——› cirrhosis • Palpable mass ——› abscess or malignancy • A liver span >15 cm ——› fatty infiltration, congestion other infiltrative diseases, or malignancy • Liver tenderness ——› acute disease but is generally not helpful • The presence of a friction rub or bruit ——› malignancy.

17. Physical Examination • Spider angioma • palmar erythema • distended abdominal veins • jaundice • Ascites • jaundice • Ascites indicate cirrhosis Acute hepatitis Cirrhosis Malignancy

18. Physical Examination • Splenomegaly • A palpable, distended gallbladder ——› malignant biliary obstruction • Asterixis • Fever Infections Infiltrative diseases Fulminant hepatic failure End-stage liver disease Billiary colic Infection

19. hyperbilirubinemia

20. Diagnosis The alkaline phosphatase level • When normal → extrahepatic obstruction is unlikely • When level is more than three times the normal → cholestasis or extrahepatic obstruction • When markedly elevated together with bilirubin, a common bile duct stone should be excluded • An elevated level, but with a normal bilirubin may occur in the presence of a partial extrahepatic or intrahepatic obstruction

21. Diagnosis • G-Glutamyltransferase • Elevated in patients with • Hepatobiliary disease, • Alcohol intake • Protein levels • Help to differentiate acute from chronic liver disease. • Elevated globulin with hypoalbuminemia supports the diagnosis of cirrhosis • Prothrombin time • Hypercholesterolemia often is seen in patients with cholestasis • Urine tests • Bilirubin • Urobilinogen

22. Diagnosis Second-line tests for jaundice • 5-nucleotidase • leucine aminopeptidase • antinuclear antibody • Anti smooth muscle antibody • Immunoglobulins • antimitochondrial antibody • hepatitis serologies • a1-antitrypsin • iron levels • Ceruloplasmin • a-fetoprotein

23. Diagnosis • Radiological tests: • Ultrasonography • Stones • Billiary ductal dilatation • Tumour masses, lymph nods etc. • Organomegaly • AsciCtes • CT scan abdomen • Endoscopic Retrograde Cholangiopancreatography (ERCP) • Liver Biopsy

24. Acetominophen Alcohol Amiodarone Azulfidine Carbenicillin Clindamycin Colchicine Cyclophosphamide Diltiazem Ketoconazole Methyldopa Niacin Nifedipine NSAIDs Propylthiouracil Pyridium Pyrazinamide Quinidine Rifampicin Salicylates Verapamil Common Drugs Associated With Hyperbilirubinemia HEPATOCELLULAR CAUSES

25. Amitriptyline Androgenic steroids (B) Atenolol Augmentin Azathioprine Bactrim (D) Benzodiazeprines Captopril Carbamazole Chlordiazepoxide (D)) Clofibrate Coumadin Cyclosporine Danazol (B) Dapsone Disopyramide Erythromycin Estrogens (B) Ethambutol Floxuridine 5-Flucytosine Fluoroquinolones Griseofulvin Haloperidol (D) Labetolol Nicotinic acid NSAIDs Penicillins Phenobarbital Phenothiazines (D) Phenytoin Tamoxifen Tegretol Thiabendazole (D) Thiazides Thiouracil Tolbutamide (D) Tricyclics (D) Verapamil Zidovudine Common Drugs Associated With Hyperbilirubinemia CHOLESTATIC CAUSES B. bland or noninflammatory cholestasis: D. ductopenic cholestasis or vanishing bile duct syndrome.

27. Acetohexamide Allopurinol Ampicillin Augmentin Cimetidine Dapsone Disulfiram Gold Hydralazine Lovostatin Nitrofurantoin NSAIDs Phenytoin Rifampicin Thiouracil Tetracycline Common Drugs Associated With Hyperbilirubinemia MIXED CAUSES

28. Diagnosis of hyperbilirubinemia. • Patient's history • Physical examination • Laboratory tests