Week 3 P&I Flashcards

1
Q

How much alcohol is a unit?

A

8g in the UK

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2
Q

What will the majority of alcohol abusers develop?

A

Steatosis

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3
Q

What can steatosis progress to?

A

Steatohepatitis

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4
Q

What percentage of alcohol abusers will develop cirrhosis?

A

10-20%

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5
Q

What is cirrhosis?

A

a combination of fibrosis and nodule development and regenerative tissue trying to regenerate in these nodules

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6
Q

What turns alcohol into acetaldehyde in the central pathway of alcohol metabolism?

A

ADH - Alcohol dehydrogenase

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7
Q

What turns acetaldehyde into acetate in the central pathway of alcohol metabolism?

A

ALDH - Acetaldehyde dehydrogenase

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8
Q

What are the two side pathways of alcohol metabolism?

A
  1. MEOS - microsomal ethanol oxidising system

2. Catalase

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9
Q

What enzyme is used in the MEOS pathway of alcohol metabolism?

A

CYP2E1

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10
Q

Where does the catalase pathway take place for alcohol metabolism?

A

Peroxisomes

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11
Q

What is a product of both side pathways of alcohol metabolism?

A

ROS - reactive oxygen species

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12
Q

What happens if there is excess of alcohol in the main metabolic pathway?

A

The central pathway can’t handle it by itself so it begins to go to the side pathways.

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13
Q

What are the consequences of acetaldehyde production?

A
  • Binds to proteins and DNA –> prevents transcription of DNA
  • Stimulates collagen production by Stellate cells
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14
Q

What are the consequences of acetate production?

A

Increased acetyl co-A promotes inflammation by histone acetylation –> prevents transcription

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15
Q

What are the consequences of increased NADH/NAD ratio?

A

Increased fatty acid synthesis; reduced fatty acid oxidation which promotes steatosis

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16
Q

What are the consequences of non-oxidative metabolism of alcohol?

A

Fatty acid ethyl ester production: promotes steatosis

17
Q

What is the issue with more NADH going to the ETC in alcohol metabolism?

A

the ETC leaks electrons as well as producing ATP which produces superoxide ions and peroxidase and ultimately the most potent free radical the hydroxyl radical

18
Q

What is the negative effect of the ETC leaking electrons?

A

The radicals created damage cell membranes and interrupt DNA transcription

19
Q

What is the effect of TNF-a production?

A

Promotes apoptosis and necrosis, and activates stellate cells to produce collagen leading to fibrosis

20
Q

What does increased intestinal permeability in chronic alcohol exposure cause?

A

Portal circulation endotoxemia

21
Q

What cells are activated in Portal circulation endotoxemia?

A

Kupffer cells are constantly stimulated and produce more pro-inflammatory cytokines and ROS as well, which in turn promote liver injury

22
Q

What is the intrinsic pathway of apoptosis initiated by?

A

Oxidative stress

23
Q

What is the extrinsic pathway of apoptosis initiated by?

A

TNF-a

24
Q

What do proteolytic caspases do?

A

Degrade cellular organelles

25
Q

What is the main difference between apoptosis and necrosis?

A
Apoptosis = natural cell death 
Necrosis = traumatic cell death
26
Q

what can vitamin deficiency in Chronic alcohol excess lead to?

A

impaired metobolism of methionine and reduction in glutathione

27
Q

What are the consequences of disrupted methionine metabolism?

A

-Reduced SAM: SAH ratio
• Reduced transmethylation; impaired gene expression
• Increased Caspase-3/8 expression
o APOPTOSIS
• Increased TNF production (reduced IL-10)
o INFLAMMATION
• Reduced Cystathionine β-synthase activity
- Reduced Trans-sulfuration
• Reduced Glutathione production
o OXIDATIVE STRESS

28
Q

What effect can obesity have in chronic excess of alcohol?

A

the enzyme that metabolises excess alcohol cytochrome P4502E1 is also induced so more POS

29
Q

What are the histological findings in fatty liver?

A

Predominantly macrosteatosis in zone 2 and 3

30
Q

What are the histological findings in Alcoholic hepatitis?

A

Swollen hepatocytes, giant mitochondria, steatosis, collagen in zone 3

31
Q

What are the histological findings in Alcoholic cirrhosis?

A

Classically micronodular with or without alcoholic hepatitis

32
Q

What is fibroscan - transient elastography used for?

A

To measure the stiffness/firmness of the liver

33
Q

What are the essential features of ‘clinically relevant’ Alcoholic Hepatitis?

A
  • recent excess alcohol (within 8 weeks)
  • Bilirubin > 80mol/l (onset within 8 weeks)
  • exclusion of other liver disease
  • AST < 500 (AST: ALT ratio >1.5)
34
Q

What are the main things that impact the progression of damage to the liver by alcohol?

A

Nutrition and obesity