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APPROACH TO JAUNDICE Dr.

TRJ Nadala JAUNDICE icterus Yellow discoloration of the skin and tissues resulting from the deposition of bilirubin. Occurs only in the presence of hyperbilirubinemia CLINICAL PRESENTATION OF JAUNDICE SERUM BILIRUBIN 1-1.5 mg/dL = normal concentrations; no discoloration of skin and sclerae <5% conjugated forms >3 mg/dL jaundice becomes evident Jaundice is less apparent is dark skinnedindividuals but you may look at the tongue when you are in doubt. Estimation of Degree of Serum Bilirubin by Physical Examination Sclera icterus Serum bilirubin at Icterus under tongue least 3mg/dL Icteric skin higher level of bilirubin conjugated in the serum URINE BILIRUBIN Always conjugated Implies liver disease When you look at tea-colored urine in a patient with jaundice, always remember that urine bilirubin is always conjugated because it is water-soluble. CLINICAL HISTORY: Risk Factors for Liver Disease RISK FACTORS Family history ASSOCIATED LIVER DISEASE Metabolic problems such as: Hemochromatosis Wilsons Disease Alcohol Liver Disease 10/13/11 Medications Foreign travel Ulcerative Colitis History of jaundice or hepatitis Hepatobiliary surgery

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Drug-induced Liver Injury Hepatitis A Primary Sclerosing Cholangitis Chronic Hepatitis Cirrhosis Iatrogenic cause Post-op stricture of bile ducts Recurrent bile stones These are only simplistic ways by which you can arrive at your differential diagnoses. Bear in mind that coexisting liver problems can occur in patients with multiple risk factors. Autoimmune disease come to mind only when you have ruled out other causes of hepatitis PBC (primary biliary cirrhosis) also an autoimmune problem; presents more as cholestasis Drug-induced liver injury usually attributed to herbal preparations (e.g. KOI herbal capsule); may even lead to renal injury. THE RISK IS REAL. DO NOT TAKE THEM! LABORATORY TESTS

Alcohol consumption (usually 50g/dL) Hyperlipidemia Fatty Liver Blood transfusion Hepatitis B, C Parenteral exposure to illicit IV drug use Health workers Male homosexuality Autoimmune disease Autoimmune Hepatitis PBC

Serum enzymes that reflect damage to hepatocytes SGPT/ALT (alanine aminotransferase) SGOT/AST (aspartate aminotransferase) - Found in cardiac, skeletal, kidneys, brain, pancreas, lungs, leukocytes, erythrocytes - Anything that involves these organs can also give rise to AST elevations ALT is the more specific enzyme. Serum enzymes that reflect cholestasis Alkaline phosphatase 5nucleotidase Gamma glutamyl transpeptidase Request for alkaline phosphatase first. If elevated, request for the next two to confirm that alkaline phosphatase is hepatic in origin. Tests that measure biosynthetic function of the liver Serum albumin Prothrombin time These two parameters represent how the liver synthesizes its function.

SERUM ALBUMIN Synthesized exclusively in hepatocytes Long half-life (15-20 days) therefore not an indicator of Acute or Mild Hepatic Dysfunction

APPROACH TO JAUNDICE Dr. TRJ Nadala When serum albumin is low and there are no other causes of hypoalbuminemia, this suggests a liver problem that has already been going on in a chronic fashion. In acute injuries, albumin levels can stay normal for 21 days and will only be reflective of low synthetic capacity if the disease entity has gone beyond that point. Non-hepatic causes of hypoalbuminemia: Protein malnutrition Protein-losing enteropathies Nephrotic syndrome Infections with prolonged increased in IL-1 and/or TNF SERUM PROTHROMBIN TIME Measures Factor II, V, VII, X (these are the vitamin K dependent factors) Shorter serum half-lives, therefore is the single best acute measure of hepatic synthetic function Drops earlier than albumin levels when the liver is no longer functioning. Prolonged in: Hepatitis Cirrhosis Vitamin K deficiency obstructive jaundice; fat malabsorption Poor prognostic sign therefore >5 sec above control not corrected by Vit. K. Connotes hepatic cell injury Evaluation of the Patient with Jaundice 10/13/11

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Isolated Bilirubin means only bilirubin is increased. All other values are normal. Direct bilirubin there is conjugation occurring in the liver, but the excretion is the problem causing the direct bilirubin to be absorbed in the system and reflect as elevated. Indirect bilirubin no conjugation occurs Crigler-Najjar syndrome leads to failure to thrive so this is hardly seen in adults. Gilberts syndrome is more common. Really, they are normal they just get jaundiced every now and then.

Hepatocellular pattern (liver enzymes are more elevated than alkaline phosphatase) this means that a liver injury is a probable cause of the jaundice. Cholestatic pattern (alkaline phosphatase is more elevated than liver enzymes) Liver Test Patterns in Hepatobiliary Disorders ACUTE HEPATOCELLULAR NECROSIS (viral, drug hepatitis, hepatotoxins, acute heart failure) Both fractions may be elevated Bilirubin Peak follows aminotransferases Bilirubinuria present Elevated > 500 IU Aminotransferase ALT>AST Alkaline phosphatase Normal to <3x N Albumin Normal Prothrombin time Usually normal

APPROACH TO JAUNDICE Dr. TRJ Nadala If >5x N & not corrected by Vit. K, it suggests poor prognosis CHRONIC HEPATOCELLULAR NECROSIS Both fractions may be elevated Bilirubin Bilirubinuria present Aminotransferase Elevated <300 IU Alkaline phosphatase Normal to <3x N Albumin Often decreased Often proloned Prothrombin time Fails to correct with parenteral Vitamin K ALCOHOLIC HEPATITIS CIRRHOSIS Both fractions may be elevated Bilirubin Bilirubinuria present Aminotransferase AST:ALT >2 Alkaline phosphatase Normal to <3x N Albumin Often decreased Often prolonged Prothrombin time Fails to correct with parenteral Vitamin K INTRA- AND EXTRA- HEPATIC CHOLESTASIS OBSTRUCTIVE JAUNDICE Both fractions may be elevated Bilirubin Bilirubinuria present Normal to moderate elevation Aminotransferase Rarely >500 IU Alkaline phosphatase Elevated >4x N Albumin Normal, unless chronic Normal Prothrombin time If prolonged; will correct with parenteral Vitamin K. INFILTRATIVE DISEASE (tumor, granuloma) PARTIAL BILE DUCT OBSTRUCTION Bilirubin Usually normal Aminotransferase Normal to slight elevation Elevated >4x N Alkaline phosphatase Fractionate, confirm liver origin with 5nucleotidase or GGT Albumin Normal Prothrombin time Normal Audio * In the tables, Doc Nadala said that we should take note of the details in BOLD type. 10/13/11

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REST IF YOU MUST BUT NEVER QUIT.