CRACKCast E028 – Jaundice

In CRACKCast, Podcast by Adam Thomas1 Comment

This episode of CRACKCast covers Rosen’s Chapter 28, Jaundice.

Show Notes – Link HERE

1) Describe heme metabolism

Jaundice = elevated serum bilirubin

Conjugated bilirubin = direct bilirubin

Unconjugated bilirubin = indirect bilirubin (can cross blood brain barrier) – does not bind albumin

  • unconjugated levels of bilirubin that is not bound to albumin is able to cross the blood-brain barrier and leads to adverse neurologic effects
    • developmental abnormalities, encephalopathy, death
    • is exacerbated by any condition that leads to increased heme production or a process that competitively decreases albumin/binds to albumin (e.g. drugs or cirrhosis)
  • conjugated bilirubin in contrast is non-toxic

Total bilirubin = direct + indirect

Normal bilirubin metabolism:

  • heme products (red blood cells) breaking down → bilirubin
    • very small portion of bilirubin comes from myoglobin (muscles) or maturing erythroid cells
  • heme products are oxidied into biliverdin → bilirubin
  • bilirubin binds to albumin, then is glucuronidated into the conjugated form in hepatocytes
  • conjugated bilirubin is excreted into the biliary system and emptied in the gut
  • colonic bacteria metabolize most conjugated bilirubin to urobilogen and stercobilin
    • stercobilin is excreted into the stool
    • urobilinogen is reabsorbed and is excreted into the urine
  • remaining conjugated bilirubin is de-conjugated and re-enters the portal circulation to be taken up again by hepatocytes
    • this completes the entero-hepatic circulation of bilirubin

Abnormal Bilirubin Metabolism

Jaundice – usually not obvious until >25 mg/L

  • seen in tissues with high albumin concentrations
    • skin, eyes,
    • absent in tears, saliva

Three pathologic processes leading to elevated bilirubin:

  1. Overproduction – high levels of heme production
    • hemolysis
    • hypoalbuminemia
    • acidemia
    • drugs (bind competitively to albumin )
  2. Failure of conjugation – hepatocytes unable to take up, conjugate and excrete bilirubin
    • hepatocellular dysfunction
  3. Decreased clearance
    • biliary excretion problem

2) List common pre-hepatic/hepatic/post-hepatic causes of jaundice

Three pathologic processes leading to elevated bilirubin:

  1. Overproduction – high levels of heme production
    • hemolysis
    • hypoalbuminemia
    • acidemia
    • drugs (bind competitively to albumin )
  1. Failure of conjugation – hepatocytes unable to take up, conjugate and excrete bilirubin
    • hepatocellular dysfunction
      1. Toxins
        • Tylenol, ETOH
      2. Vascular:
        • Budd-Chiari
      3. Inflammatory/ Infectious
        • Viral – Hepatitis
        • Autoimmune
      4. Pregnancy related: HELLP / acute fatty liver
  1. Decreased clearance –
    • biliary excretion problem
      1. Gallstone disease : CBD stone, ascending cholangitis

Wisecracks:

1) What are clinical signs of liver disease?

Abnormalities in bilirubin metabolism:

  • Jaundice – usually not obvious until >25 mg/L
    • seen in tissues with high albumin concentrations:
      • skin, eyes,
      • absent in tears, saliva

Symptoms:

  • May be asymptomatic or have:
    • pruritus, malaise, nausea
  • Jaundice with abdominal pain = biliary obstruction or hepatic inflammation
  • Jaundice WITHOUT abdominal pain = pancreatic neoplasm
  • Ask about fit of clothing (ascites) or personality changes

Signs:

  • Skin
    • Sublingual or conjunctival jaundice
  • Signs of liver disease:
    • angiomas, excoriations, caput medusae, ascites, liver borders and texture, splenomegaly, neurologic examination, asterixis
  • Stages of encephalopathy – see table in Rosen’s

2) What laboratory tests can be useful in a jaundiced patient?

  • GGT = confirms a hepatic source of ALP if ALP is up
    • ALP can also be elevated from bone or placental sources
  • An elevated reticulocyte count can suggest hemolysis
  • Acetaminophen level*** (AST is first to rise)
  • Glucose level
  • Ammonia level – is of limited use and does NOT correlate with degrees of hepatic encephalopathy
  • Ascitic fluid – for analysis
  • Blood cultures – for fever
  • INR , PTT
  • AST, ALT

3) List the triad of acute hepatic failure

  • Jaundice
  • Encephalopathy
  • Coagulopathy (INR > 1.5)

4) List and describe 6 critical causes of jaundice

  1. Hepatic
    • Fulminant hepatic failure
    • Toxin
    • Virus
    • Alcohol
    • Ischemic insult
    • Reye’s syndrome
  2. Biliary
    • Cholangitis (ascending infectious)
  3. Systemic
    • Sepsis
    • Heatstroke
  4. Cardiovascular
    • Obstructing AAA
    • Budd-Chiari syndrome
    • Severe congestive heart failure
  5. Heme-oncologic
    • Transfusion reaction (hemolysis)
  6. Reproductive
    • Pre-eclampsia or HELLP syndrome
    • Acute fatty liver of pregnancy

Empirical management

  • Depends on the cause of jaundice and problem:
    • Bleeding (in the context of coagulopathy)
      • Transfuse PRBC’s and FFP
    • Spontaneous bacterial peritonitis
      • >250 PMN’s per cm3 of ascitic fluid
        • IV ceftriaxone
      • Acetaminophen toxicity:
        • N-acetylcysteine
      • Ascending cholangitis
        • Antibiotics
        • ***need acute biliary drainage in 24-48 hrs because most antibiotics are excreted***
      • Choledocolithiasis or strictures
        • Need for ERCP
        • ***neither CT or U/S is 100% sensitive for choledocolithasis, but a dilated CBD highly suggests obstruction***
      • Immune-mediated hemolytic anemia:
        • Transfuse only if unable to oxygenate and in discussion with hematology
        • Remove any potential offending drugs in the case of G6PD

5) What are 3 causes of jaundice in pregnancy?

  • Pregnancy and jaundice = pathology
    • Potential causes:
    • 1) hyperemesis gravidarum
      • In the first trimester – ?poor nutrition and impaired bilirubin excretion
      • Can have VERY high transaminases (20x ULN)
      • Trxt: fluids and antiemetics and admission if biochemically deranged
    • 2) acute fatty liver of pregnancy
      • In the 3rd trimester
      • Due to microvascular fat accumulation in the liver
      • S+s:
        • Nausea, vomiting, anorexia, jaundice
      • May progress to fulminant hepatic failure
      • Trxt: delivery, patients may need liver transplant!
    • 3) intrahepatic cholestasis of pregnancy
      • Idiopathic cause of jaundice in 2-3rd trimester
      • S+s:
        • Pruritis – trunk, extremities, palms, soles.
        • Acholic stools and dark urine
      • Increased risk of preterm labour or early fetal demise intra-uterine.
      • Trxt:
        • Ursodiol, cholestyramine
        • Vitamin K

This post was copyedited by Rob Carey (@_RobCarey)

(Visited 1,069 times, 1 visits today)
Adam Thomas

Adam Thomas

CRACKCast Co-founder and newly minted FRCPC emergency physician from the University of British Columbia. Currently spending his days between a fellowship in critical care and making sure his toddler survives past age 5.
Adam Thomas
- 1 day ago
Chris Lipp
Chris Lipp is one of the founding Fathers for CrackCast. He currently divides his time as an EM Physician in Calgary (SHC/FMC) and in Sports Medicine. His interests are in endurance sports, exercise as medicine, and wilderness medical education. When he isn’t outdoors with his family, he's brewing a coffee or dreaming up an adventure…..