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Everything You Need to Know About Jaundice
- 2. Jaundice Overview • Definition • Production & metabolism • Measurement of bilirubin – serum & urine • Approach to the patient • Broad Differential Diagnosis • Work-up for “Medical” Jaundice • Work-up if Obstructive Jaundice
- 3. Jaundice Definition • Yellowish discoloration of tissue resulting from the deposition of bilirubin in hyperbilirubinemia. • Detected by examining sclerae – ELASTIN • Scleral icterus -serum bilirubin of 3.0 mg/Dl • As serum bilirubin levels rise skin yellow in light-skinned &green if long-standing, oxidation of bilirubin to biliverdin.
- 4. Jaundice Differential diagnosis for yellowing of skin : • Drugs – quinacrine, phenols. • Carotenoderma -ingest excessive amounts of carotene. palms, soles, forehead, and nasolabial folds. sparing of the sclerae.
- 5. Jaundice Production and Metabolism of Bilirubin: • Bilirubin, a tetrapyrrole pigment. Bilirubin 70-80%-senescent RBC HEMOPROTIENS- Myoglobin,cytochromes
- 6. Jaundice Production steps: Bilirubin formed in RES 1.Opening of heme ring Formation of Biliverdin by Microsomal enzyme 2.Biliverdin BILIRUBIN by Cytosolic enz. (Insoluble in plasma)
- 7. Jaundice • To be transported in blood, bilirubin must be solubilized by noncovalent binding to albumin. • Bilirubin + albumin= unconjugated bilirubin transported to liver. • Bilirubin minus albumin enters hepatocyte.
- 8. Jaundice UNCONJ. Bilirubin Urobilinogen (80-90% excreted in feces) 10-20% portal circulation & reexcreted in liver
- 9. Jaundice Measurement of Serum Bilirubin • van den Bergh reaction- direct- and indirect • the normal serum bilirubin is <1 mg/dL • Up to 30% of the total may be direct-reacting (conjugated) bilirubin
- 10. Jaundice Measurement of Urine Bilirubin • Unconjugated bilirubin is always bound to albumin in the serum -not filtered by the kidney-not found in the urine. • Conjugated bilirubin is filtered at the glomerulus and the majority is reabsorbed by the proximal tubules; a small fraction is excreted in the urine • Any bilirubin found in the urine is conjugated bilirubin. The presence of bilirubinuria implies the presence of liver disease
- 11. Jaundice Approach to the Patient: JAUNDICE
- 12. Jaundice History,physical exam.,lab tests- s.bilirubin,LFT,PT, Albumin Isolated hyperbilirubinemiia Indirect-DRUGS- Rifampicin, INHERITED – G ilberts,Crigler Najjar,,Hemolytic dis.., Direct>15% - inherited disorders e.g- Dubin johnson syn.,Rotor’s syn. Bilirubin & LFT 1.Hepatocellular- ALT/AST>>ALP 2.CHOLESTATIC— ALP>>>>ALT/AST
- 13. Jaundice Hepatocellular Conditions that May Produce Jaundice Viral hepatitis – Viral serology, ALT>=AST Hepatitis A, B, C, D, and E Epstein-Barr virus Cytomegalovirus Herpes simplex Alcohol – AST/ALT -2:1,AST rarely > 300 Drug toxicity Predictable, dose-dependent, e.g., acetaminophen Unpredictable, idosyncratic, e.g., isoniazid Environmental toxins Vinyl chloride Jamaica bush tea—pyrrolizidine alkaloids Kava Kava Wild mushrooms—Amanita phalloides or A. verna Wilson's disease – young adult males where no othr cause of jaundice found Autoimmune hepatitis – middle aged females,
- 14. Jaundice Initial Evaluation: History • Jaundice, acholic stools, tea-colored urine • Fever/chills, RUQ pain (cholangitis) • Could lead to life-threatening septic shock • Reasons to have hepatitis or cirrhosis? • Alcohol, Viral, risk factors for viral hepatitis • Exposure to toxins or offending drugs • Inherited disorders or hemolytic conditions • Recent blood transfusions or blood loss? • Is patient septic or on TPN? • Recent gallbladder surgery? (CBD injury)
- 15. Jaundice • While ALT and AST values less than 8 times normal may be seen in either hepatocellular or cholestatic liver disease, values 25 times normal or higher are seen primarily in acute hepatocellular diseases.
- 16. Jaundice Initial Evaluation: Physical Exam • Signs of end stage liver disease (cirrhosis) • Ascites, splenomegaly, spider angiomata, and gynecomastia • Jaundice evident first underneath the tongue, also evident in sclerae or skin • Courvoisier’s sign = painless, but palpable or distended gallbladder on exam • Could indicate malignant obstruction
- 17. Jaundice When the pattern of the liver tests suggests a cholestatic disorder, the next step is to determine whether it is intra- or extrahepatic cholestasis • Appropriate test is an ultrasound • Biliary dilatation indicates extrahepatic cholestasis – SURGICAL JAUNDICE • Absence of biliary dilatation suggests intrahepatic cholestasis
- 18. Jaundice Intrahepatic A. Viral hepatitis 1. Fibrosing cholestatic hepatitis—hepatitis B and C 2. Hepatitis A, Epstein-Barr virus, cytomegalovirus B. Alcoholic hepatitis C. Drug toxicity 1. Pure cholestasis—anabolic and contraceptive steroids 2. Cholestatic hepatitis—chlorpromazine, erythromycin estolate 3. Chronic cholestasis—chlorpromazine and prochlorperazine
- 19. Jaundice DDx: Unconjugated bilirubinemia • ↑production • Extravascular hemolysis • Extravasation of blood into tissues • Intravascular hemolysis • Errors in production of red blood cells • Impaired hepatic bilirubin uptake(trnsport) • CHF • Portosystemic shunts • Drug inhibition: rifampin, probenecid
- 20. Jaundice DDx: Unconjugated bilirubinemia • Impaired bilirubin conjugation • Gilbert’s disease • Crigler-Najarr syndrome • Neonatal jaundice (this is physiologic) • Hyperthyroidism • Estrogens • Liver diseases • chronic hepatitis, cirrhosis, Wilson’s disease
- 21. Jaundice DDx: Conjugated Bilirubinemia • Intrahepatic cholestasis/impaired excretion • Hepatitis (viral, alcoholic, and non-alcoholic) • Any cause of hepatocellular injury • Primary biliary cirrhosis or end-stage liver dz • Sepsis and hypoperfusion states • TPN • Pregnancy • Infiltrative dz: TB, amyloid, sarcoid, lymphoma • Drugs/toxins i.e. chlorpromazine, arsenic • Post-op patient or post-organ transplantation • Hepatic crisis in sickle cell disease
- 22. Jaundice DDx: Obstructive Jaundice • Obstructive Jaundice– extrahepatic cholestasis • Choledocholithiasis (CBD or CHD stone) • Cancer (peri-ampullary or cholangioCA) • Strictures after invasive procedures • Acute and chronic pancreatitis • Primary sclerosing cholangitis (PSC) • Parasitic infections • Ascaris lumbricoides, liver flukes
- 23. Jaundice Screening Labs • NL LFT r/o hepatic injury or biliary tract dz • Consider inherited disorders or hemolysis • ↑Alk Phos moreso than AST/ALT implies “cholestasis” (intrahepatic vs obstruction) • ↑Alk Phos also seen in sarcoid, TB, bone • In this case, GGT is specific for biliary origin • Predominant ↑AST/ALT implies intrinsic hepatocellular disease • AST/ALT ratio > 2 in alcoholic hepatitis • ↓albumin or ↑INR c/w advanced liver dz
- 24. Jaundice Subsequent Labs • If no concern for obstructive jaundice: • Viral (Hep B&C) serologies for viral hepatitis • anti-mitochondrial Ab (PBC) • anti-smooth muscle Ab (Auto-immune) • iron studies (hemochromatosis) • ceruloplasmin (Wilson’s) • Alpha-1 anti-trypsin activity (for deficiency)
- 25. Jaundice Imaging for Obstructive Jaundice • RUQ Ultrasound • See stones, CBD diameter • CT scan • Identify both type & level of obstruction • ERCP • Direct visualization of biliary tree/panc ducts • Procedure of choice for choledocholithiasis • Diagnostic –AND- therapeutic (unlike MRCP) • PTC useul of obstruction is prox to CHD • Endoscopic Ultrasound or EUS
- 26. Jaundice Treatment • If Medical, then treat the etiology • If Obstructive Jaundice: • Should r/o ascending cholangitis, ABC/resusc • For cholangitis: IVF, IV Antibiotics, Decompression • Stones (remove stones vs stent vs drainage) • Done via ERCP or PTC or open (surgery) • Benign stricture (stent vs drainage catheter) • Cancer (Stent vs drainage +/- resect the CA)
- 27. Jaundice Thanks