Lec 26

Question 1

What is the definition of acute liver failure [3 parts/values]?

Answer 1

• coagulopathy [INR > 1.5]
• encephalopathy
• jaundice < 24 wks duration

no underlying chronic liver disease

Question 2

What is fulminant vs subfulminant acute liver failure?

Answer 2

fulminant = encephalopathy < 8 weeks

sub-fulminant = encephalopathy > 8 weeks

Question 3

Most common cause of acute liver failure worldwide?

Answer 3

acute Hep B

Question 4

Most common cause of acute liver failure in the US?

Answer 4

acetaminophen

Question 5

What is pathophysiology of cerebral edema in hepatic failure?

Answer 5

• excess NH3 to brain –> interacts wtih glutamate to form glutamine = has osmotic effect to draw water in

Question 6

What is the difference hepatic encephalopathy and cerebral edema in hepatic failure?

Answer 6

hepatic encephalopahy = reversible chemical state

cerebral edema = physical condition of excess H20 in brain; occurs with late stages of hepatic encephalopathy

Question 7

What is leading cause of death in patients with fulminant hepatic failure?

Answer 7

cerebral edema

Question 8

What type of organisms primarily seen in sepsis with acute liver failure?

Answer 8

usually gram positive within 3 days of ICU stay

see fungal infections 2 wks after

Question 9

What immuno defects in acute liver failure?

Answer 9

kupffer cell malfunction = macrophages of the liver

neutrophil malfunction

cell mediated immunity

Question 10

What is pathophys of cardio dysfunction in acute liver failure?

Answer 10

• low systemic and pulm vascular resistance with compensatory increase in CO and metabolic rate –> leads to tissue hypoxia and lactic acidosis production

Question 11

What are signs of cardiac dysfunction in liver failure?

Answer 11

• hypotension and tachycardia

- lactic acidsosi

Question 12

What is mech of renal failure in liver failure?

Answer 12

• direct nephrotoxicity OR hepatorenal syndrome

Question 13

What is hepatorenal syndrome?

Answer 13

• renal vasoconstriction secondary to systemic vasodilation seen in fulminant hepatic failure
• functional abnormality but reversible with liver recovery/transplant

Question 14

What clinical features of hepatorenal syndrome?

Answer 14

• increased BUN and creatinine
• decreased urine output

with background of hepatic failure

Question 15

What is mech of hypoglycemia in liver failure?

Answer 15

• defective gluconeogenesis

- inadequate hepatic uptake of insulin

Question 16

What is treatment for acute liver failure due to tylenol toxicity?

Answer 16

N-acetylcysteine [NAC]

Question 17

What is treatment for acute liver failure due to mushroom?

Answer 17

penicillin G

Question 18

What zone of liver affected by acetaminophen?

Answer 18

centrilobular zone 3

Question 19

What is clinical presentation of acetaminophen induced fulminant hepatic failure?

Answer 19

• N/V, ab pain
• ALT/AST up to 10,000 within 12-24 hrs
• long PT/INR

Question 20

What is kings criteria for acetaminophen induced acute liver failure?

Answer 20

pH < 7.3 
OR
- grade 3/4 encephalopathy
- INR > 6.5
- serum creatinine > 3.4

Question 21

What types of drugs implicated in acute liver failure?

Answer 21

• antibiotics
• herbals
• CNS drugs

Question 22

What is effect of ALT/AST rice alone or ALT/AST + bilirubin elevation on prognosis?

Answer 22

worse prognosis if have bilirubin AND high ALT/AST

Question 23

What is normally the part of drug that causes hepatic injury?

Answer 23

the activtiy metabolite after phase 1 oxidation by CYP450

Question 24

What are some things that induce CYP?

Answer 24

rifampin
phenytoin
carbamazepine
phenobarbital
dexamethasone
alcohol

Question 25

How does alcohol use make acetaminophen liver tox worse?

Answer 25

because alcohol induces cyp450 –> more toxic metabolic

Question 26

When do you get hepatotoxicity with isoniazid?

Answer 26

usually after 1wk - 6 motnhs = have a latent period

Question 27

What drug is a common cause of cholestatic hepatotoxicity?

Answer 27

amoxicillin/clavulanic acid [augmentin]