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18-3 Flashcards

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1
Q

What usually mediates injury with Drug/Toxin Induced Liver Injury?

A

Reactive metabolites that are generated in the liver

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2
Q

What enzyme family is involved in most of the metabolic reactions that occur in the liver with Drug/Toxin Induced Liver Injury?

A

CYP450

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3
Q

Where are CYP450 enzymes the most active in the liver and what is the result?

A

Most active in the central zone of the lobule

== Zone 3 injury of hepatocytes

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4
Q

Morphologic finding of toxicity due to Acetaminophen?

A

Hepatocellular Necrosis

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5
Q

Morphologic findings of toxicity due to Anabolic Steroids?

A

Cholestatic without inflammation and vascular lesions

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6
Q

Morphologic finding of toxicity due to Aspirin (Reyes Syndrome)?

A

Fatty liver (microvesicular steatosis)

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7
Q

What agents can cause Hepatocellular Adenoma?

A

Oral contraceptives

Anabolic Steroids

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8
Q

What agents can cause Hepatocellular Carcinoma?

A

Alcohol

Thorotrast

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9
Q

What agent can cause Cholangiocarcinoma?

A

Thorotrast

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10
Q

What agents can cause Angiosarcoma?

A

Thorotrast

Vinyl Chloride

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11
Q

Drug-induced Liver Injury can be due to what 2 types?

A
  1. Dose dependent direct hepatotoxins

2. Idiosyncratic

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12
Q

Which type of Drug-induced liver injury is the most common and what are example agents?

A

Idiosyncratic:

  • Antimicrobial
  • Cardiovascular, CNS, Antineoplastic and analgesic agents
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13
Q

What are risk factors for Alcohol Liver Disease?

A

Gender - females are more susceptible
Ethnicity - Black and Asian populations
Co-morbid conditions

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14
Q

Why are females more susceptible to Alcohol Liver Disease?

A

Estrogen increases gut permeability to endotoxins

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15
Q

Why are Asian populations more susceptible to Alcohol Liver Disease?

A

ALDH*2 (Aldehyde Dehydrogenase) mutation

= Intolerant to alcohol – flushing, nausea

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16
Q

Overall cascade of Alcohol Liver Disease?

A

Steatosis (fatty liver)
Alcohol Hepatitis
Cirrhosis

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17
Q

How does Steatosis develop with Alcohol Liver Disease?

A
  • Alcohol metabolism generates NADH
  • NADH favors lipogenesis in hepatocytes
    = Fatty liver
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18
Q

What 3 factors can contribute to Alcohol Hepatitis?

A
  1. Acetaldehyde
  2. CYP2E1 increases ROS
  3. Methionine metabolism impairment
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19
Q

If Alcohol (+) CYP450, what does that cause?

A

Conversion of other drugs to toxic metabolites

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20
Q

With Alcohol Liver Disease, list the symptoms at each main step

A

Steatosis - asymptomatic with hepatomegaly
Alcoholic Hepatitis - jaundice, RUQ pain, hepatomegaly
Cirrhosis

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21
Q

Lab levels with Alcohol Liver Disease at the Alcoholic Hepatitis stage?

A

AST:ALT = 2:1

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22
Q

What qualities make up Metabolic Syndrome?

A
  1. Diabetes/glucose issues/insulin resistance
    * 2 of the following:
    - BP > 140/90
    - Central obesity
    - Dyslipidemia
    - Microalbuminemia
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23
Q

What is the most common cause of chronic liver disease?

24
Q

What is the most common cause of chronic liver disease?

25
What is NAFLD?
Presence of hepatic steatosis WITHOUT excessive alcohol consumption = fatty liver without contributing it to alcohol
26
A majority of patients with NAFLD will only develop?
Fatty liver and nothing else
27
What is NAFLD associated with?
Metabolic syndrome and obesity | insulin resistance
28
NASH
Nonalcoholic Steatohepatitis | - similar to alcoholic hepatitis
29
NASH
Nonalcoholic Steatohepatitis | - similar to alcoholic hepatitis
30
What is NASH?
NAFLD patients with steatohepatic injury with histology features similar to alcoholic hepatitis
31
NASH patients are at an increased risk of developing?
Fibrotic liver disease
32
NASH diagnosis requires a?
Biopsy
33
What is seen on the morphology with NASH?
Steatosis Lobular inflammation Ballooned hepatocytes
34
With NAFLD, fibrosis develops around the?
Central vein = spider web of collagen deposition
35
How does Fibrosis turn into Cirrhosis with NAFLD?
- Fibrosis around the central vein - Periportal fibrosis - Bridging fibrosis - Cirrhosis
36
Pediatric NAFLD morphology?
Increased steatosis and portal fibrosis | Decreased ballooned hepatocytes
37
Symptoms of NAFLD?
Asymptomatic -- metabolic syndrome presentations
38
Symptoms of NASH?
Asymptomatic OR | RUQ pain, fatigue, hepatomegaly
39
What usually causes death with NASH patients?
Cardiovascular disease or HCC
40
What is mutated with Hemochromatosis?
``` HFE mutation (c282y) = cytosine to tyrosine substitution == DECREASED HEPCIDIN = Increased iron absorption ```
41
What is mutated with Hemochromatosis?
``` HFE mutation (c282y) = cytosine to tyrosine substitution == DECREASED HEPCIDIN = Increased iron absorption ```
42
Symptoms of Hemochromatosis?
Heart failure Diabetes Bronze skin Cirrhosis with hepatomegaly
43
Morphology items with Hemochromatosis?
Prussian blue stain shows hemosiderin deposition | Brown/black liver due to iron
44
Wilson disease mutation?
ATP7B gene mutation
45
Symptoms of Wilson Disease?
``` - copper issues Hemolytic anemia Neuro/psych involvement Acute/Chronic liver disease Kayser-fleischer rings in eye ```
46
Symptoms of Wilson Disease?
``` - copper issues Hemolytic anemia Neuro/psych involvement Acute/Chronic liver disease Kayser-fleischer rings in eye ```
47
Alpha1 Antitrypsin mutation?
PiZZ mutation = Glutamine to Lysine substitution
48
Alpha1 Antitrypsin mutation?
PiZZ mutation = Glutamine to Lysine substitution
49
Disorder of protein folding that causes it to accumulate in liver?
Alpha1 Antitrypsin Deficiency
50
Normal job of Alpha1 Antitrypsin?
(-) proteases
51
Which proteases are allowed to run wild with Alpha1 Antitrypsin deficiency?
Neutrophil elastase Cathepsin G Proteinase 3
52
Symptoms of Alpha1 Antitrypsin deficiency?
Hepatitis, jaundice, pulmonary emphysema
53
Morphologic changes with Alpha1 Antitrypsin deficiency?
Cytoplasmic globular hepatocyte inclusions | = (+) PAS and diastase resistant
54
Morphologic changes with Alpha1 Antitrypsin deficiency?
Cytoplasmic globular hepatocyte inclusions | = (+) PAS and diastase resistant
55
What is the most common inherited hepatic disorder in children?
Alpha1 Antitrypsin Deficiency

GI - 2 (61 decks)

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