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PATH30001 - Mechanisms of Disease > Lecture 3 - Alcohol Mediated Injury > Flashcards

Lecture 3 - Alcohol Mediated Injury Flashcards

1
Q

What are the ways that toxic substances can get in to the body?

A

Skin
Lungs
GI tract

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1
Q

What types of disease are caused by alcohol?

A

Steatosis
Alcohol hepatitis
Cirrhosis

NB alcohol has effects all over the body

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2
Q

What is the toxin in alcohol?

A

Ethanol

But predominantly: Acetaldehyde (metabolite of ethanol)

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3
Q

What is the difference in terms of effect on the body with alcohol consumed in great and small amounts?

A 
Great amounts:
 • brain dysfunction
 • chronic gastritis
 • pancreatitis
 • cardiomyopathy

In moderation
 • increased fibrinolyses
 • decreased thrombosis
 • increased HDL
 • decreased atherosclerosis formation
 • decreased osteoporosis
 • decreased kidney stone formation
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4
Q

Which cancers does alcohol cause?

A

Mouth
Larynx
Liver
etc.

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5
Q

Describe metabolism of alcohol in the liver

A
  • CYPs
  • alcohol dehydrogenase
  • catalase
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6
Q

Describe the absorption of alcohol

A
  1. Consumption
  2. Absorbed directly through GIT
  3. Blood stream
  4. Metabolism in the liver
  5. Excretion
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7
Q

Compare ADH levels in men and women

A

Men have more ADH than women

Alcohol dehydrogenase

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8
Q

Where are CYPs in the hepatocytes?

A

Microsomes / smooth ER

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9
Q

Where is ADH in hepatocytes?

A

Cytosol

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10
Q

What is the role of the peroxisomes?

A

Location of catalase

Metabolism of alcohol

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11
Q

What are some harmful biproducts of alcohol metabolism?

A

Reactive oxygen species
Free radicals
NADH

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12
Q

List the order of parts of the brain affected by alcohol

A

The cortex: higher order functions
Limbic system: emotions, memory
Cerebellum: motor control
Lower brain stem: breathing, BP

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13
Q

What is ethanol predominantly metabolised into?

A

Acetaldehyde

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14
Q

At what blood alcohol level leads to coma/fatal respiratory arrest?

A

0.3-0.4 gl/dl

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15
Q

What is another name for ‘sleepiness’?

A

Narcosis

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16
Q

Describe the effects of alcohol on the stomach

A

Acute gastritis
• acute inflammation
• haemorrhage
• sloughing of mucosa

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17
Q

What are some chronic effects of alcohol?

A
  • Alcoholism
  • Altered fatty acid metabolism
  • Steatosis
  • Hepatitis
  • Cirrhosis
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18
Q

What changes occur to hepatocytes due to fatty acids?

A

‘Fatty liver’
Many small lipid droplets in the cytoplasm of the liver
Reversible

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19
Q

What are some acute effects of alcohol?

A
  • ‘Party syndrome’ (effects on CNS)
  • Acute gastritis
  • Steatosis
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20
Q

Describe the changes to fatty acid metabolism due to chronic alcohol consumption

A

Increased synthesis of:
• Fatty acids
• Triglycerides
• Ketone bodies

Increased deposition of dietary fatty acids in the hepatocytes (in the cytoplasm)

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21
Q

Describe the changes to fatty acid metabolism due to chronic alcohol consumption.
Why is this bad?

A 
Increased synthesis of:
 • Fatty acids
 • Triglycerides
 • Ketone bodies
Reduction in:
 • Proteins which absorb triglycerides (such as lipoproteins and apoproteins)

Increased deposition of dietary fatty acids in the hepatocytes (in the cytoplasm)

Bad because:
• Ketone bodies are inherently toxic
• There is increased fatty acids circulating in the body

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22
Q

What is hepatitis?

Reversible?

A

Inflamed liver
Early exposure
Reversible

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23
Q

What is alcoholism?

A

Chronic consumption of doses great enough to injure socially, mentally, physically

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24
Describe the structure of a liver lobule
* hexagonal * ventral hepatic venule * branches of hepatic portal vein * bile ducts * branches of hepatic artery * connective tissue
25
Under what conditions does cirrhosis occur?
Continued exposure to alcohol | Progresses from steatosis or hepatitis
26
What is the microscopic unit of the liver?
Liver lobule
27
Describe blood flow in a liver lobule
From the border, into the central venule
28
Which structure is very important for the stability of the liver lobule?
Connective tissue
29
Compare histology of fatty liver with a healthy liver
* lipid droplets | * fibrotic tissue
30
Which structure in the liver is most at risk during chronic alcohol consumption?
Connective tissue
31
What are Kupffer cells?
Resident macrophages in the liver
32
What causes the inflammation in hepatitis?
Cytokine release from Kupffer cells
33
What is cirrhosis?
``` A combination of : • necrosis • inflammation • fibrosis • regeneration ``` There is a finite number of times that the liver tissue can be damaged and regenerate.
34
What are 'new epitopes' in cirrhosis?
Brought about by changes caused by acetaldehyde | Induce immune response
35
What are the green spots in cirrhosis?
* fibrotic tissue | * bile accumulation
36
What are Mallory bodies? | What is their role in hepatitis ?
Intermediate filaments They are a histological feature of hepatitis. They stain pink.
37
Why does hepatocellular carcinoma occur?
Continuous regeneration involves much cell proliferation | In some cess, this leads to carcinoma
38
Describe the function of nodules in liver cirrhosis
Non functional
39
Describe the function of Stellate cells
Once activated, they proliferate into myofibroblasts that lay down much fibrotic tissue • fibrogenesis • contraction (scarring...)
40
Which cell responds to the cytokines from Kupffer cells?
Stellate cells | These are there liver stem cells
41
What is the effect of alcohol on pulmonary immunity?
Decreased immunity | More prone to infection
42
Describe what happens to the connection between hepatic portal veins and central venues during liver cirrhosis
Fibrotic connection, instead of sinusoids between cells
43
What are there effects of alcohol on other organs?
Pancreatitis Wernicke syndrome Foetal alcohol syndrome
44
What is the main way that toxic substances are introduced to our bodies?
1. Compound introduced to our bodies 2. Metabolism, to form toxic metabolites → Toxicity
45
What are some cytotoxic pharmaceuticals?
* paracetamol * therapeutic drugs * aspirin * oral contraceptives
46
What are some recreational drugs that introduce toxic substances to our bodies?
* cigarettes * alcohol (ethanol) * recreational drugs: cocaine, heroin etc.
47
What are the ways that toxins cause damage?
* direct covalent binding * toxic metabolite formation * free radical formation
48
What types of disease are cirrhosis, fatty liver syndrome, and hepatitis?
Tissue remodelling
49
What are CYPs?
Cytochrome P450 enzymes in the liver
50
What types of disease are cirrhosis, steatosis, and hepatitis?
Tissue remodelling
51
Which molecule elicits the acute effects of alcohol?
Acetaldehyde
53
Which chronic conditions of the liver are reversible, and which are irreversible?
``` Reversible: • steatosis • hepatitis Irreversible: • cirrhosis ```
53
What are the features of steatosis?
* lipid droplets in cytoplasm of hepatocytes | * perivenular fibrosis
55
Why does alcohol cause hepatitis?
* increased ROS * lipid peroxidation * decreased glutathione * mitochondrial damage * cytokine release from Kupffer cells
55
What are the symptoms of alcoholic hepatitis?
* jaundice * liver tenderness * fever
56
What is glutathione?
The major antioxidant in the body
57
What are the changes occurring in hepatitis?
* necrosis * neutrophil infiltrate * perivenular fibrosis
58
What effect does acetaldehyde have on the cytoskeleton?
Acetaldehyde forms complexes with protein, which disrupt the cytoskeleton and membrane
59
What is fibrosis and when does it occur?
It is a process whereby collagen is laid down | It occurs in response to injury
61
What processes do the cytokines released by Kupffer cells bring about?
* Chemotaxis * Contraction * Hepatocyte death * Proliferation * Fibrogenesis
62
Where do dietary fatty acids accumulate with chronic alcohol consumption?
In the cytoplasm of hepatocytes

PATH30001 - Mechanisms of Disease (34 decks)

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