Lecture 22: Acute Liver Failure Flashcards Preview

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Flashcards in Lecture 22: Acute Liver Failure Deck (41):
1

Acute liver failure: triad

Coagulopathy (INR > 1.5), encephalopathy, jaundice

2

Two types of acute liver failure

Fulminant and subfulminant (longer jaundice)

3

Etiologies of acute liver failure: major classes

Viral, drugs/toxins, vascular causes, metabolic, misc (autoimmune, mets)

4

Viruses of acute liver failure

HAV, HBV, HDV, HEV, HSV, CMV, EBV, VZ, adeno, hemorrhagic fever viruses

5

Drugs of acute liver failure

Acetaminophen, mushroom poisoning, ecstasy and idiosyncratic

6

Vascular causes of acute liver failure

Budd-chiari (clot)

7

Metabolic causes of acute liver failure

Wilson's, acute fatty liver of pregnancy, pediatric diseases

8

Outcomes of acute liver failure (%)

45% survive, 25% transplant, 30% death

9

What kind of patients do not do well w/out liver transplant; who does well?

Wilson's, drug-induced, indetermined; acetominophen

10

Causes of mortality in acute liver failure

Hepatic encephalopathy (number one cause), infection, hypoglycemia, coagulopathy, renal failure

11

Why do we get hepatic encephalopathy

High serum levels of NH3 (not metabolized into urea) --> crosses BBB + glutamate --> glutamine --> astrocyte accumulation and brain swelling (cerebral edema)

12

Stages of hepatic encephalopathy

Stage I = subtle changes; stage II = drowsiness, asterixis (hand flapping); stage III = incoherent, sleeping; stage IV = coma w/ cerebral edema

13

Cerebral edema: clinical signs

Cushing reflex (systemic HTN/bradycardia, end-stage response related to brain herniation), decerebrate rigidity, disconjugate eye movements, loss of pupillary reflexes

14

Acute liver failure: coagulopathy (why?)

Due to loss of clotting factors, especially Factor V, and platelet abnormalities

15

Acute liver failure: infection (why, mortality)

Kupffer cell impairment, neutrophil malfunction, decreased compliment levels; NUMBER TWO CAUSE OF MORTALITY

16

Blood pressure, heart rate, and acidity in acute liver failure

Hypotension, tachycardia, lactic acidosis due to decreased perfusion

17

Acute liver failure and renal failure

Complicates 50% of cases: can be direct nephrotoxicity (tylenol) or hepatorenal syndrome --> renal vasoconstriction (response to systemic vasodilation) can cause poor perfusion

18

Acute liver failure and metabolic changes (one word)

Hypoglycemia

19

ALF: tylenol, give...

N-Acetylcysteine

20

ALF: amanita poisoning, give...

Penicilli G

21

ALF: HSV, give...

Acyclovir

22

ALF: autoimmune, give...

Steroids (?)

23

ALF: pregnancy, give...

Delivery

24

Describe acetaminophen liver failure

Too much --> reactive intermediates (NAPQI), can be metabolized via conjugation with glutathione, which is replaced by cysteine (so give N-Acetylcysteine)

25

King's college criteria (transplant): acetaminophen

pH less 7.3 (due to high lactic acid) or grade III-IV encephalopathy, high INR, renal failure = 80% mortality

26

King's college criteria (transplant): non-acetaminophen

High INR or younger than 10, older than 40, bad etiology (Wilson's), high bilirubin, or jaundice greater than 7 days

27

What is the most common cause of acute liver failure in the US?

Drug toxicity

28

Hy's Law (prognosis)

If you have drug induced liver injury with elevations in AST/ALT AND bilirubin, this is worse than AST/ALT alone (JAUNDICE IS WORSE)

29

What does idiosyncratic drug hepatoxicity mean? (note: these are opposite from predictable hepatoxicity)

Doesn't matter the dose, you can get liver injury, variable duration to injury, may have extrahepatic involvement, but low incidence

30

Liver drug metabolism: phases

Phase I = oxidation via cytochrome system; Phase II = conjugation via transferases (now hydrophilic); Phase III = excretion

31

After which phase do you often get a toxic metabolite?

After Phase I, which generates an active metabolite that can cause hepatic injury

32

Drugs that induce CYP

Rifampin, phenytoin, carbamazepine, phenobarbital, dexamethasone, alcohol

33

Drugs that inhibit CYP

Grapefruit juice, erythromycin, clarithromycin, ketoconazole, ritonavir

34

Alcohol and acetaminophen

Heavy drinker w/ alcohol on board: as alcohol leaves bloodstream w/ up-regulated CYP2E1 (due to alcohol) you metabolize tylenol faster, so you have TWO THINGS: DELAYED PRESENTATION AND INCREASED TOXICITY

35

What can restrict rate of drug elimination?

Depleted cofactors, which can happen during fasting (like an alcoholic who hasn't been eating who takes too much tylenol)

36

Describe phase III

Takes place in hepatocytes via ATP-binding cassette transport protein (requires energy)

37

Acetaminophen: minimal hepatotoxic dose, tx

7.5 g (~15 ES tylenol), activated charcoal w/ in 4 hours and NAC w/ in 8 hours

38

Idiosyncratic hepatotoxins: mechanisms (2)

1. Metabolic idiosyncrasy (genetic differences); 2. Immunoallergy

39

Isoniazid: mechanism, frequency, latency, % mortality

Metabolic idiosyncrasy with high frequency, hepatitis develops latency w/ 10% mortality

40

Dilantin: frequency, % mortality, clinical features

Rare, high mortality (up to 40%), features can include fever, rash, immune reaction

41

Amoxicillin/clavulanic acid (augmentin): frequency, presentation, risk factor

Most frequently reported ab associated with DILI, cholestatitic hepatitis, immunologic idiosyncrasy (HLA haplotype)