Evaluation of a patient Evaluation of a patient with Jaundicewith Jaundice

Dr Yousif. A QariDr Yousif. A QariAssist prof. consultant Assist prof. consultant

gastroenterologistgastroenterologistKAUH, Jeddah, Saudi ArabiaKAUH, Jeddah, Saudi Arabia

Definition of JaundiceDefinition of Jaundice

Jaundice, as in the French Jaundice, as in the French jaune,jaune, refers to the refers to the yellow discoloration of the skin.yellow discoloration of the skin.

It arises from the abnormal accumulation of It arises from the abnormal accumulation of bilirubin in body tissues, which occurs when the bilirubin in body tissues, which occurs when the serum bilirubin level exceeds 3 mg/dL or 50 serum bilirubin level exceeds 3 mg/dL or 50 mmol/L. mmol/L.

Laboratory Tests

Total and direct bilirubin assays

.

Conjugated hyperbilirubinemia

Unconjugated hyperbilirubinemia

Causes Of Hyperbilirubinemia

UNCONJUGATED FORM

HemolysisHemolysis Glucose-6-phosphate Glucose-6-phosphate

deficiencydeficiency Pyruvate kinase deficiencyPyruvate kinase deficiency DrugsDrugs

Ineffective erythropoiesisIneffective erythropoiesis

Neonatal causesNeonatal causes Physiologic abnormalitiesPhysiologic abnormalities Lucy-Driscoll syndromeLucy-Driscoll syndrome Breast milkBreast milk

Uridine diphosphate Uridine diphosphate glucuronosyltransferase glucuronosyltransferase deficienciesdeficiencies

Gilbert syndromeGilbert syndrome Crigler-Najjar syndromes (I Crigler-Najjar syndromes (I

and II)and II)

Miscellaneous causesMiscellaneous causes DrugsDrugs HypothyroidismHypothyroidism ThyrotoxicosisThyrotoxicosis Pulmonary infarctPulmonary infarct FastingFasting

Causes Of Hyperbilirubinemia

CONJUGATED FORM

Congenital causesCongenital causes Rotor syndromeRotor syndrome Dubin-Johnson syndromeDubin-Johnson syndrome Choledochal cystsCholedochal cysts

Familial disordersFamilial disorders Benign recurrent Benign recurrent

intrahepatic cholestasisintrahepatic cholestasis Cholestasis of pregnancyCholestasis of pregnancy

Hepatocellular defectsHepatocellular defects Alcohol abuseAlcohol abuse Viral infectionViral infection

SepsisSepsis

CholestaticCholestatic Primary biliary cirrhosisPrimary biliary cirrhosis Primary sclerosing Primary sclerosing

cholangitischolangitis Biliary obstructionBiliary obstruction Pancreatic diseasePancreatic disease

Systemic diseaseSystemic diseaseInfiltrative disordersInfiltrative disordersPostoperative Postoperative complicationscomplicationsRenal diseaseRenal diseaseDrugsDrugs

Several questions must be answered initiallySeveral questions must be answered initially

1. Is the elevated bilirubin conjugated or unconjugated?1. Is the elevated bilirubin conjugated or unconjugated? 2. If the hyperbilirubinemia is unconjugated, is it caused by 2. If the hyperbilirubinemia is unconjugated, is it caused by

increased productionincreased production decreased uptakedecreased uptake impaired conjugationimpaired conjugation

3. If the hyperbilirubinemia is conjugated, is the problem 3. If the hyperbilirubinemia is conjugated, is the problem intrahepatic or intrahepatic or extrahepatic?extrahepatic?

4. Is the process acute or chronic? 4. Is the process acute or chronic?

Conjugated hyperbilirubinemiaConjugated 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.

CholestasisCholestasis

Chronic cholestasis may arise from 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.Acute disease. New-onset bilirubinuriaNew-onset bilirubinuria Fever Fever Right upper quadrant pain,Right upper quadrant pain, Tenderness,Tenderness, Hepatomegaly, Hepatomegaly,

Investigation of a patient with jaundiceInvestigation of a patient with jaundice

History of presentationHistory of presentation

Medication useMedication use

Past medical historyPast medical history

Physical examinationPhysical examination

Evaluation of liver function testsEvaluation of liver function tests

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

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.

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.

History

Age:

< 30 years ——› acute parenchymal disease

> 65 years ——› stones or malignancies

30 - 50 years ——› chronic liver disease

Children and young adults ——› viral hepatitis

HistorySex:

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

Physical Examination

Examination of the liverExamination 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

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.

Physical Examination

Spider angiomapalmar erythemadistended abdominal veins jaundiceAscites

jaundiceAscites

indicate cirrhosis

Acute hepatitis Cirrhosis Malignancy

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

hyperbilirubinemia

LFTLFT Hepatocellular disease.

Cholestatic disease.

Bilirubin levels Usually variableUsually variable

Usually < 5mg/dLUsually < 5mg/dL

Usually highUsually high

consistently > 5 mg/dL

Aminotransferases Variable, depending Variable, depending on the underlying on the underlying disease disease

Mild to modMild to mod

Usually < 400 IU/mLUsually < 400 IU/mL

Alkaline phosphatase

Usually Normal - mildUsually Normal - mild Usually > 3 times (N)Usually > 3 times (N)

DiagnosisDiagnosis

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

DiagnosisDiagnosis

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

DiagnosisDiagnosis

Second-line tests for jaundice

5-nucleotidaseleucine aminopeptidaseantinuclear antibodyAnti smooth muscle antibodyImmunoglobulinsantimitochondrial antibodyhepatitis serologiesa1-antitrypsiniron levelsCeruloplasmina-fetoprotein

DiagnosisDiagnosis

Radiological tests:

Ultrasonography

Stones

Billiary ductal dilatation

Tumour masses, lymph nods etc.

Organomegaly

AsciCtes

CT scan abdomen

Endoscopic Retrograde Cholangiopancreatography (ERCP)

Liver Biopsy

Common Drugs Associated With Hyperbilirubinemia

AcetominophenAcetominophenAlcoholAlcoholAmiodaroneAmiodaroneAzulfidineAzulfidineCarbenicillinCarbenicillinClindamycinClindamycinColchicineColchicineCyclophosphamideCyclophosphamideDiltiazemDiltiazemKetoconazoleKetoconazoleMethyldopaMethyldopa

NiacinNiacinNifedipineNifedipineNSAIDsNSAIDsPropylthiouracilPropylthiouracilPyridiumPyridiumPyrazinamidePyrazinamideQuinidineQuinidine RifampicinRifampicinSalicylatesSalicylatesVerapamilVerapamil

HEPATOCELLULAR CAUSESHEPATOCELLULAR CAUSES

Common Drugs Associated With Hyperbilirubinemia

AmitriptylineAmitriptylineAndrogenic steroids (Androgenic steroids (BB))AtenololAtenololAugmentinAugmentinAzathioprineAzathioprineBactrim (Bactrim (DD))BenzodiazeprinesBenzodiazeprinesCaptoprilCaptoprilCarbamazoleCarbamazoleChlordiazepoxide (Chlordiazepoxide (D))D))ClofibrateClofibrateCoumadinCoumadinCyclosporineCyclosporineDanazol (Danazol (BB))DapsoneDapsoneDisopyramideDisopyramideErythromycinErythromycin Estrogens (Estrogens (BB)) EthambutolEthambutolFloxuridineFloxuridine

5-Flucytosine5-FlucytosineFluoroquinolonesFluoroquinolonesGriseofulvinGriseofulvinHaloperidol (Haloperidol (DD))LabetololLabetololNicotinic acidNicotinic acidNSAIDsNSAIDsPenicillinsPenicillinsPhenobarbitalPhenobarbitalPhenothiazines (Phenothiazines (DD))PhenytoinPhenytoinTamoxifenTamoxifenTegretolTegretolThiabendazole (Thiabendazole (DD))ThiazidesThiazidesThiouracilThiouracilTolbutamide (Tolbutamide (DD))Tricyclics (Tricyclics (DD))VerapamilVerapamilZidovudineZidovudine

CHOLESTATIC CAUSES

B. bland or noninflammatory cholestasis: D. ductopenic cholestasis or vanishing bile duct syndrome.

Common Drugs Associated With Hyperbilirubinemia

AcetohexamideAcetohexamideAllopurinolAllopurinolAmpicillinAmpicillinAugmentinAugmentinCimetidineCimetidineDapsoneDapsoneDisulfiramDisulfiramGoldGold

HydralazineHydralazineLovostatinLovostatinNitrofurantoinNitrofurantoinNSAIDsNSAIDsPhenytoinPhenytoinRifampicinRifampicinThiouracilThiouracilTetracyclineTetracycline

MIXED CAUSES

Diagnosis of hyperbilirubinemia.

PPatient's history

Physical examination

Laboratory tests