toxic hepatocellular injury l.
Download
Skip this Video
Download Presentation
Toxic Hepatocellular Injury

Loading in 2 Seconds...

play fullscreen
1 / 14

Toxic Hepatocellular Injury - PowerPoint PPT Presentation


  • 136 Views
  • Uploaded on

Toxic Hepatocellular Injury. Mike Contarino , MD Internal Medicine and Pediatrics 1/22/10. Liver Injury Patterns. Hepatocellular Elevated aminotransferases +/- alk phos, bili Cholestasis Elevated alk phos, bili +/- aminotransferases Isolated Hyperbilirubinemia Jaundice if bili >2.5

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Toxic Hepatocellular Injury' - tanaya


Download Now An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
toxic hepatocellular injury

Toxic Hepatocellular Injury

Mike Contarino, MD

Internal Medicine and Pediatrics

1/22/10

liver injury patterns
Liver Injury Patterns
  • Hepatocellular
    • Elevated aminotransferases +/- alk phos, bili
  • Cholestasis
    • Elevated alk phos, bili +/- aminotransferases
  • Isolated Hyperbilirubinemia
    • Jaundice if bili >2.5
  • Infiltrative
    • Elevated Alk Phos; Bili/ALT/AST nl
hepatocellular pattern
Hepatocellular Pattern
  • Viral Hepatitis: A, B, C, (ED), CMV, EBV, HSV, VZV
  • Autoimmune hepatitis
  • Drugs and Toxins: EtOH, Acetaminophen, Meds
  • NAFLD: Obese, DM, Hyperlipidemia
  • Vascular/Ischemic: Hypotension, CHF, Budd Chiari
  • Hereditary: Often systemic - Hemochromatosis, Alpha 1 antitrypsin def, Wilson’s Dx, Celiac
toxic hepatocellular injury6
Toxic Hepatocellular Injury
  • COMMON MEDS
    • ACETAMINOPHEN
    • NSAIDS
    • STATINS
    • ANTIBIOTICS (especially Amox/Clav)
some specifics
SOME SPECIFICS
  • ALT- more specific for liver than AST
  • >1000 indicative of ischemia, tylenol, severe viral hepatitis.
  • ALT> AST viral or fatty, AST:ALT >2:1 EtOH
  • Elevated LDH: ischemic or toxic
mechanism for drug excretion
Mechanism for drug excretion
  • Phase I and phase II reactions metabolize drugs
    • Phase I- Cytochrome P450 (oxidases, CYP3A4)
    • make polar for water solubility
    • Phase II- UDP glucoronyltransferases (UGT1, UGT2)
  • Products excreted via transport on canalicularor sinusoidal membranes (Phase III)
    • Transport into bile
dili drug induced liver injury
DILI- Drug Induced Liver Injury
  • Requires high index of suspicion
  • CLASSIFICATION:
    • Clinical: Hepatocellular, cholestatic, or mixed
    • Mechanism: Direct vs Idiosyncratic (immune/ metabolic)
    • Histology: Necrosis/apoptosis, Steatosis, Fibrosis, SOS (sinusoidal obstruction syndrome), Granulomatous
mechanism of dili
Mechanism of DILI
  • Intrinsic hepatotoxins- dose dependent hepatocellular necrosis
  • Idiosyncratic reactions- most common
    • 0.01 to 1 percent of people taking drug
    • Allergic- hypersensitivity reaction
    • Metabolic- aberrant metabolism in susceptible pts
variables
VARIABLES
  • EtOH- CYP induction, GSH depletion
  • Diet-
    • CYP induction- Brussel sprouts, cabbage, broccoli, high protein diet
    • CYP inhibition- grapefruit juice, malnutrition
  • Other drugs- VAST!!
    • Alcohol and drugs do not mix!
  • Age- Decrease in CYP activity
  • Genetics, Underlying liver disease
sooo our patient
Sooo…. Our Patient
  • Markedly Elevated AST/ALT, mild AlkPhos, nlbili, Increased LDH
    • Toxic vs Ischemic
    • Not AST:ALT >2, No tylenol
    • ? In setting of early fatty liver, EtOH, and hx of paroxysmal atrial tachycardia
  • Biopsy: Stage 1 fibrosis of portal tracts, no steatosis or cholestasis, rare inflammatory cells. Resolving toxic-metabolic injury.
  • Ischemic 2/2 shock liver thought most likely
  • ? Holter monitor