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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
Q

Describe the structure of a liver lobule

A
  • hexagonal
  • ventral hepatic venule
  • branches of hepatic portal vein
  • bile ducts
  • branches of hepatic artery
  • connective tissue
25
Q

Under what conditions does cirrhosis occur?

A

Continued exposure to alcohol

Progresses from steatosis or hepatitis

26
Q

What is the microscopic unit of the liver?

A

Liver lobule

27
Q

Describe blood flow in a liver lobule

A

From the border, into the central venule

28
Q

Which structure is very important for the stability of the liver lobule?

A

Connective tissue

29
Q

Compare histology of fatty liver with a healthy liver

A
  • lipid droplets

* fibrotic tissue

30
Q

Which structure in the liver is most at risk during chronic alcohol consumption?

A

Connective tissue

31
Q

What are Kupffer cells?

A

Resident macrophages in the liver

32
Q

What causes the inflammation in hepatitis?

A

Cytokine release from Kupffer cells

33
Q

What is cirrhosis?

A 
A combination of :
 • necrosis
 • inflammation
 • fibrosis
 • regeneration

There is a finite number of times that the liver tissue can be damaged and regenerate.

34
Q

What are ‘new epitopes’ in cirrhosis?

A

Brought about by changes caused by acetaldehyde

Induce immune response

35
Q

What are the green spots in cirrhosis?

A
  • fibrotic tissue

* bile accumulation

36
Q

What are Mallory bodies?

What is their role in hepatitis ?

A

Intermediate filaments

They are a histological feature of hepatitis. They stain pink.

37
Q

Why does hepatocellular carcinoma occur?

A

Continuous regeneration involves much cell proliferation

In some cess, this leads to carcinoma

38
Q

Describe the function of nodules in liver cirrhosis

A

Non functional

39
Q

Describe the function of Stellate cells

A

Once activated, they proliferate into myofibroblasts that lay down much fibrotic tissue
• fibrogenesis
• contraction
(scarring…)

40
Q

Which cell responds to the cytokines from Kupffer cells?

A

Stellate cells

These are there liver stem cells

41
Q

What is the effect of alcohol on pulmonary immunity?

A

Decreased immunity

More prone to infection

42
Q

Describe what happens to the connection between hepatic portal veins and central venues during liver cirrhosis

A

Fibrotic connection, instead of sinusoids between cells

43
Q

What are there effects of alcohol on other organs?

A

Pancreatitis
Wernicke syndrome
Foetal alcohol syndrome

44
Q

What is the main way that toxic substances are introduced to our bodies?

A
  1. Compound introduced to our bodies
  2. Metabolism, to form toxic metabolites
    → Toxicity
45
Q

What are some cytotoxic pharmaceuticals?

A
  • paracetamol
  • therapeutic drugs
  • aspirin
  • oral contraceptives
46
Q

What are some recreational drugs that introduce toxic substances to our bodies?

A
  • cigarettes
  • alcohol (ethanol)
  • recreational drugs: cocaine, heroin etc.
47
Q

What are the ways that toxins cause damage?

A
  • direct covalent binding
  • toxic metabolite formation
  • free radical formation
48
Q

What types of disease are cirrhosis, fatty liver syndrome, and hepatitis?

A

Tissue remodelling

49
Q

What are CYPs?

A

Cytochrome P450 enzymes in the liver

50
Q

What types of disease are cirrhosis, steatosis, and hepatitis?

A

Tissue remodelling

51
Q

Which molecule elicits the acute effects of alcohol?

A

Acetaldehyde

53
Q

Which chronic conditions of the liver are reversible, and which are irreversible?

A 
Reversible:
 • steatosis
 • hepatitis
Irreversible:
 • cirrhosis
53
Q

What are the features of steatosis?

A
  • lipid droplets in cytoplasm of hepatocytes

* perivenular fibrosis

55
Q

Why does alcohol cause hepatitis?

A
  • increased ROS
  • lipid peroxidation
  • decreased glutathione
  • mitochondrial damage
  • cytokine release from Kupffer cells
55
Q

What are the symptoms of alcoholic hepatitis?

A
  • jaundice
  • liver tenderness
  • fever
56
Q

What is glutathione?

A

The major antioxidant in the body

57
Q

What are the changes occurring in hepatitis?

A
  • necrosis
  • neutrophil infiltrate
  • perivenular fibrosis
58
Q

What effect does acetaldehyde have on the cytoskeleton?

A

Acetaldehyde forms complexes with protein, which disrupt the cytoskeleton and membrane

59
Q

What is fibrosis and when does it occur?

A

It is a process whereby collagen is laid down

It occurs in response to injury

61
Q

What processes do the cytokines released by Kupffer cells bring about?

A
  • Chemotaxis
  • Contraction
  • Hepatocyte death
  • Proliferation
  • Fibrogenesis
62
Q

Where do dietary fatty acids accumulate with chronic alcohol consumption?

A

In the cytoplasm of hepatocytes

PATH30001 - Mechanisms of Disease (34 decks)

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