Lecture 22: Acute Liver Failure Flashcards

1
Q

Acute liver failure: triad

A

Coagulopathy (INR > 1.5), encephalopathy, jaundice

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2
Q

Two types of acute liver failure

A

Fulminant and subfulminant (longer jaundice)

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3
Q

Etiologies of acute liver failure: major classes

A

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

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4
Q

Viruses of acute liver failure

A

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

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5
Q

Drugs of acute liver failure

A

Acetaminophen, mushroom poisoning, ecstasy and idiosyncratic

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6
Q

Vascular causes of acute liver failure

A

Budd-chiari (clot)

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7
Q

Metabolic causes of acute liver failure

A

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

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8
Q

Outcomes of acute liver failure (%)

A

45% survive, 25% transplant, 30% death

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9
Q

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

A

Wilson’s, drug-induced, indetermined; acetominophen

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10
Q

Causes of mortality in acute liver failure

A

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

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11
Q

Why do we get hepatic encephalopathy

A

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

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12
Q

Stages of hepatic encephalopathy

A

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

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13
Q

Cerebral edema: clinical signs

A

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

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14
Q

Acute liver failure: coagulopathy (why?)

A

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

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15
Q

Acute liver failure: infection (why, mortality)

A

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

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16
Q

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

A

Hypotension, tachycardia, lactic acidosis due to decreased perfusion

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17
Q

Acute liver failure and renal failure

A

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

18
Q

Acute liver failure and metabolic changes (one word)

A

Hypoglycemia

19
Q

ALF: tylenol, give…

A

N-Acetylcysteine

20
Q

ALF: amanita poisoning, give…

A

Penicilli G

21
Q

ALF: HSV, give…

22
Q

ALF: autoimmune, give…

A

Steroids (?)

23
Q

ALF: pregnancy, give…

24
Q

Describe acetaminophen liver failure

A

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)