Alcoholic Liver Disease L22

Question 1

~15% of alcohol metabolism takes place in the ____1____ wall. The lesser amount of gastric alcohol ____2____ in females is one reason why they become drunker quicker.

NAD+ and NADH are both drivers of oxidative stress in the liver and therefore cellular damage.

Answer 1

1. Stomach
2. Dehydrogenase

Question 2

The liver receives a greater exposure to consumed ____1____ than other organs due to direct blood flow from the upper GI tract via the ____2____ vein.

Answer 2

1. Alcohol
2. Portal

Question 3

Toxic effects of alcohol are mediated either by the direct effect of alcohol itself, or through the effects of alcohol ______.

Answer 3

Oxidation

Question 4

Alcohol is also metabolised by cytochrome P450 enzymes (as well as alcohol dehydrogenase). Isoenzyme Cytochrome P450-2E1 is the mediator of alcohol ____1____ because it is up-regulated in frequent drinkers leading them to metabolise it ____2____.

Answer 4

1. Tolerance
2. Quicker/faster

Question 5

Paracetamol is a very common cause of liver damage and is probably the most common cause of acute liver ____1____ in the UK. Because it is metabolised CYP2E1 (1^st step of its metabolism), individuals who drink heavily are at a ____2____ risk of paracetamol toxicity.

Answer 5

1. Failure
2. Greater

Question 6

What is a normogram used for?

Answer 6

To determine whether someone needs an antidote for paracetamol poisoning or not.

Question 7

Where is the damage to the liver caused by CYP2E1 induction the greatest?

Answer 7

CYP2E1 causes the most damage to the areas of the liver with the lowest oxygen levels.

Question 8

State the 2 aspects of the chronic effects of alcohol.

Answer 8

• Direct toxic effects
• ‘Empty’ calorie effects – many calories in alcohol lead to heavy drinkers being malnourished in they; a. spend money on alcohol and not food, b. are full therefore do not eat other foods leading to a low nutrient diet.

Question 9

What is the diagnosable difference between NAFLD and ALD?

Answer 9

Whether the patient states they are a heavy drinker or not.

(The differences are indistiguishable down a microscope).

Question 10

What is the best treatment for ALT?

Answer 10

Abstinence

Question 11

In the UK, how long does a patient have to abstinent for before they qualify for a lover transplant?

Why? (2)

Answer 11

6 months.

• A proportion of individuals (even if they have cirrhosis) will recover sufficiently in 6 months to not require a transplant.
• To ensure the individual is able to go without alcohol (which will be required indefinitely)

Question 12

Alcohol is directly toxic to ______ in the gut and can therefore reduce the ability to absorb nutrients.

Answer 12

Villi

Question 13

What is the first manifestation of ALD?

Answer 13

Steatosis

Question 14

Define steatosis.

Answer 14

Fat build-up within the liver cells.

Question 15

Stellate cells normally store Vitamin _1_ but when they become activated they contract and lay down collagen and ____2____ tissue within the liver.

Answer 15

1. A
2. Scar

Question 16

Define cirrhosis.

Answer 16

A chronic disease of the liver marked by degeneration of cells, inflammation, and fibrous thickening of tissue.

Question 17

Physical signs of chronic LD

Yellow = ____1____

____2____ spots = Spider naevae (people can have normally but there is an increasing number with ALD)

____3____ of the hands = Palmer Erythema

Bending of the little finger = Dupuytren’s ____4____

Enlarged ____5____ and spleen

Very swollen belly = ____6____

Answer 17

1. Jaundice
2. Red
3. Redness
4. Contracture
5. Liver
6. Ascites

Question 18

Define compensated cirrhosis.

Answer 18

Liver is scarred but there remain enough hepatocytes to keep the liver functioning sufficiently.

Question 19

Define encephalopathy.

Answer 19

Liver is no longer clearing the toxins from the blood effectively. This effects the brain and can cause confusion.

Question 20

What is Asterixis?

Answer 20

An asymmetrical jerking tremor, unlike the fine tremor caused by kidney failure.

Question 21

Define portal hypertension.

Answer 21

An increase in the blood pressure within a system of veins called the portalvenous system. Veins coming from the stomach, intestine, spleen, and pancreas merge into the portalvein, which then branches into smaller vessels and travels through the liver.

Question 22

What happens in hepato-renal syndrome?

Answer 22

As the liver is an integral part to our metabolism, once it fails it can cause a domino effect leading to failure of the kidneys and so on.

Question 23

What medicines are there for treating NAFLD and ALD?

Answer 23

There are none.

Question 24

~__% of pancreatitis is caused by high alcohol consumption.

Answer 24

70

Question 25

Define pancreatitis.

Answer 25

Inflammation of the pancreas

Question 26

Define first pass metabolism.

Answer 26

A phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation.

Question 27

Alcohol Metabolism

Question 28

Alcohol Metabolism

Question 29

Pharmacokinetics of Alcohol Consumption

• Alcohol dehydrogenase is rapidly saturated (at BAC ~10mg/1ml.
• Metabolism then follows ‘zero order (steady state) kinetics.
  
  • Approximately 1 unit/hour (8g/unit)
• The t1/2 increases as further alcohol is consumed.

Question 30

ALD Pathogenesis

Question 31

Hepatic Stellate Cell Activation

Stellate cells normally store Vitamin A but when they become activated they contract and lay down collagen and scar tissue within the liver.

Question 32

Potential therapies for ALD