Evaluation of a patient with Jaundice

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Evaluation of a patient with Jaundice

• Dr Yousif. A Qari
• Assist prof. consultant gastroenterologist
• KAUH, Jeddah, Saudi Arabia

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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.

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Laboratory Tests

• Total and direct bilirubin assays
• .

Conjugated hyperbilirubinemia
Unconjugated hyperbilirubinemia
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Causes Of HyperbilirubinemiaUNCONJUGATED FORM

• 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

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Causes Of HyperbilirubinemiaCONJUGATED FORM

• Cholestatic
• Primary biliary cirrhosis
• Primary sclerosing cholangitis
• Biliary obstruction
• Pancreatic disease
• Systemic disease
• Infiltrative disorders
• Postoperative complications
• Renal disease
• Drugs

• 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

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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?

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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.

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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,

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Investigation of a patient with jaundice

• History of presentation
• Medication use
• Past medical history
• Physical examination
• Evaluation of liver function tests

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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
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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

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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.

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History

• Age
• lt 30 years acute parenchymal disease
• gt 65 years stones or malignancies
• 30 - 50 years chronic liver disease
• Children and young adults viral hepatitis

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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

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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

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Physical Examination

• Shrunken, nodular liver may cirrhosis
• Palpable mass abscess or malignancy
• A liver span gt15 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.

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Physical Examination

• Spider angioma
• palmar erythema
• distended abdominal veins
• jaundice
• Ascites
• jaundice
• Ascites

indicate cirrhosis
Acute hepatitis Cirrhosis Malignancy
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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
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hyperbilirubinemia
LFT Hepatocellular disease. Cholestatic disease.
Bilirubin levels Usually variable Usually lt 5mg/dL Usually high consistently gt 5 mg/dL
Aminotransferases Variable, depending on the underlying disease Mild to mod Usually lt 400 IU/mL
Alkaline phosphatase Usually Normal - mild Usually gt 3 times (N)
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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

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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

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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

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Diagnosis

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

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Common Drugs Associated With Hyperbilirubinemia
HEPATOCELLULAR CAUSES

• Acetominophen
• Alcohol
• Amiodarone
• Azulfidine
• Carbenicillin
• Clindamycin
• Colchicine
• Cyclophosphamide
• Diltiazem
• Ketoconazole
• Methyldopa

• Niacin
• Nifedipine
• NSAIDs
• Propylthiouracil
• Pyridium
• Pyrazinamide
• Quinidine
• Rifampicin
• Salicylates
• Verapamil

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Common Drugs Associated With Hyperbilirubinemia
CHOLESTATIC CAUSES

• 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

• 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

B. bland or noninflammatory cholestasis D.
ductopenic cholestasis or vanishing bile duct
syndrome.
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Common Drugs Associated With Hyperbilirubinemia
MIXED CAUSES

• Acetohexamide
• Allopurinol
• Ampicillin
• Augmentin
• Cimetidine
• Dapsone
• Disulfiram
• Gold

• Hydralazine
• Lovostatin
• Nitrofurantoin
• NSAIDs
• Phenytoin
• Rifampicin
• Thiouracil
• Tetracycline

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Diagnosis of hyperbilirubinemia.

• Patient's history
• Physical examination
• Laboratory tests