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GI - 2 > 18-3 > Flashcards

18-3 Flashcards

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?

A

NAFLD

24
Q

What is the most common cause of chronic liver disease?

A

NAFLD

25
Q

What is NAFLD?

A

Presence of hepatic steatosis WITHOUT excessive alcohol consumption
= fatty liver without contributing it to alcohol

26
Q

A majority of patients with NAFLD will only develop?

A

Fatty liver and nothing else

27
Q

What is NAFLD associated with?

A

Metabolic syndrome and obesity

insulin resistance

28
Q

NASH

A

Nonalcoholic Steatohepatitis

- similar to alcoholic hepatitis

29
Q

NASH

A

Nonalcoholic Steatohepatitis

- similar to alcoholic hepatitis

30
Q

What is NASH?

A

NAFLD patients with steatohepatic injury with histology features similar to alcoholic hepatitis

31
Q

NASH patients are at an increased risk of developing?

A

Fibrotic liver disease

32
Q

NASH diagnosis requires a?

A

Biopsy

33
Q

What is seen on the morphology with NASH?

A

Steatosis
Lobular inflammation
Ballooned hepatocytes

34
Q

With NAFLD, fibrosis develops around the?

A

Central vein = spider web of collagen deposition

35
Q

How does Fibrosis turn into Cirrhosis with NAFLD?

A
  • Fibrosis around the central vein
  • Periportal fibrosis
  • Bridging fibrosis
  • Cirrhosis
36
Q

Pediatric NAFLD morphology?

A

Increased steatosis and portal fibrosis

Decreased ballooned hepatocytes

37
Q

Symptoms of NAFLD?

A

Asymptomatic – metabolic syndrome presentations

38
Q

Symptoms of NASH?

A

Asymptomatic OR

RUQ pain, fatigue, hepatomegaly

39
Q

What usually causes death with NASH patients?

A

Cardiovascular disease or HCC

40
Q

What is mutated with Hemochromatosis?

A 
HFE mutation (c282y) = cytosine to tyrosine substitution
== DECREASED HEPCIDIN = Increased iron absorption
41
Q

What is mutated with Hemochromatosis?

A 
HFE mutation (c282y) = cytosine to tyrosine substitution
== DECREASED HEPCIDIN = Increased iron absorption
42
Q

Symptoms of Hemochromatosis?

A

Heart failure
Diabetes
Bronze skin
Cirrhosis with hepatomegaly

43
Q

Morphology items with Hemochromatosis?

A

Prussian blue stain shows hemosiderin deposition

Brown/black liver due to iron

44
Q

Wilson disease mutation?

A

ATP7B gene mutation

45
Q

Symptoms of Wilson Disease?

A 
- copper issues
Hemolytic anemia
Neuro/psych involvement
Acute/Chronic liver disease
Kayser-fleischer rings in eye
46
Q

Symptoms of Wilson Disease?

A 
- copper issues
Hemolytic anemia
Neuro/psych involvement
Acute/Chronic liver disease
Kayser-fleischer rings in eye
47
Q

Alpha1 Antitrypsin mutation?

A

PiZZ mutation = Glutamine to Lysine substitution

48
Q

Alpha1 Antitrypsin mutation?

A

PiZZ mutation = Glutamine to Lysine substitution

49
Q

Disorder of protein folding that causes it to accumulate in liver?

A

Alpha1 Antitrypsin Deficiency

50
Q

Normal job of Alpha1 Antitrypsin?

A

(-) proteases

51
Q

Which proteases are allowed to run wild with Alpha1 Antitrypsin deficiency?

A

Neutrophil elastase
Cathepsin G
Proteinase 3

52
Q

Symptoms of Alpha1 Antitrypsin deficiency?

A

Hepatitis, jaundice, pulmonary emphysema

53
Q

Morphologic changes with Alpha1 Antitrypsin deficiency?

A

Cytoplasmic globular hepatocyte inclusions

= (+) PAS and diastase resistant

54
Q

Morphologic changes with Alpha1 Antitrypsin deficiency?

A

Cytoplasmic globular hepatocyte inclusions

= (+) PAS and diastase resistant

55
Q

What is the most common inherited hepatic disorder in children?

A

Alpha1 Antitrypsin Deficiency

GI - 2 (61 decks)

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