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

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

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 increased production decreased uptake decreased uptake impaired conjugation impaired conjugation 3. If the hyperbilirubinemia is conjugated, is the problem intrahepatic or intrahepatic or extrahepatic? 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, Cirrhosis, Primary sclerosing cholangitis, Primary sclerosing cholangitis, Primary biliary cirrhosis, Primary biliary cirrhosis, Secondary biliary cirrhosis, Secondary biliary cirrhosis, Carcinoma Carcinoma Drugs. Drugs. Acute disease. New-onset bilirubinuria New-onset bilirubinuria Fever Fever Right upper quadrant pain, Right upper quadrant pain, Tenderness, Tenderness, Hepatomegaly, 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 Ascending cholangitis Immediate therapy Asterixis Confusion Stupor severe hepatocellular dysfunction fulminant hepatocellular failure

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 LFT Hepatocellular disease. Cholestatic disease. Bilirubin levels Usually variable Usually < 5mg/dL Usually high consistently > 5 mg/dL Aminotransferases Variable, depending on the underlying disease Mild to mod Usually < 400 IU/mL Alkaline phosphatase Usually Normal - mild Usually > 3 times (N)

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. Common Drugs Associated With Hyperbilirubinemia AcetominophenAlcoholAmiodaroneAzulfidineCarbenicillinClindamycinColchicineCyclophosphamideDiltiazemKetoconazoleMethyldopaNiacinNifedipineNSAIDsPropylthiouracilPyridiumPyrazinamideQuinidineRifampicinSalicylatesVerapamil HEPATOCELLULAR CAUSES

25. Common Drugs Associated With Hyperbilirubinemia Amitriptyline Androgenic steroids (B) AtenololAugmentinAzathioprine Bactrim (D) BenzodiazeprinesCaptoprilCarbamazole Chlordiazepoxide (D)) ClofibrateCoumadinCyclosporine Danazol (B) DapsoneDisopyramideErythromycin Estrogens (B) EthambutolFloxuridine5-FlucytosineFluoroquinolonesGriseofulvin Haloperidol (D) Labetolol Nicotinic acid NSAIDsPenicillinsPhenobarbital Phenothiazines (D) PhenytoinTamoxifenTegretol Thiabendazole (D) ThiazidesThiouracil Tolbutamide (D) Tricyclics (D) VerapamilZidovudine CHOLESTATIC CAUSES B. bland or noninflammatory cholestasis: D. ductopenic cholestasis or vanishing bile duct syndrome.

27. Common Drugs Associated With Hyperbilirubinemia AcetohexamideAllopurinolAmpicillinAugmentinCimetidineDapsoneDisulfiramGoldHydralazineLovostatinNitrofurantoinNSAIDsPhenytoinRifampicinThiouracilTetracycline MIXED CAUSES

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