Lecture 3- alcohol induced injury Flashcards Preview

Mechanisms of human disease > Lecture 3- alcohol induced injury > Flashcards

Flashcards in Lecture 3- alcohol induced injury Deck (38):
1

what are the three ways in which alcohol is metabolised or dealt with once in the body?

It can be absorbed directly into the blood via the GIT, or it can be processed and metabolised by the liver and gastric mucosa. A small amount is lost from the body through air, sweat and urine.

2

what are the names of the three metabolic pathways for alcohol in the body?

The main one is the cytochrome P450 pathway, followed by the alcohol dehydrogenase and catalase pathways.

3

Explain alcohol metabolism according to the cytochrome P450 pathway.

The cytochrome P450 pathway occurs in the microsomes of the smooth ER of liver cells (hepatocytes) . It involves the oxidation of ethanol by the enzyme CYP2E1, to produce water. It is converted into acetylaldehyde.

4

explain alcohol metabolism according to the alcohol dehydrogenase pathway.

Ethanol is oxidised by alcohol dehydrogenase to produce acetylaldehyde, in the cytosol of gastric mucosa cells. The concentration of alcohol dehydrogenase is larger in men than women.

5

explain the alcohol metabolism according to the catalase pathway.

Peroxisomes (like lysosomes) in the liver cells take ethanol and hydrogen peroxide and converts them into acetylaldehyde and water.

6

What byproduct of alcohol metabolism is responsible for the acute effects of ethanol oxidation?

Acetylaldehyde is responsible.

7

NADH is a byproduct of alcohol metabolism. What are the acute effects of excess NADH production?

Excess NADH over NAD production causes stimulation of lipid biosynthesis (fatty liver).

8

What byproduct does CYP2E1 from the cytochrome P450 pathway produce that is harmful?

ROS are produced by CYP2E1, and they can cause mitochondrial damage to the cells of the liver.

9

what are the acute effects of alcohol consumption on the brain?

It acts as a CNS depressant, and in particular depresses inhibitory control centres such as the limbic system (emotions-memory), the cerebellum (motor control) and the lower brain stem (BP and respiration).

10

Do chronic alcoholics have a higher or lower threshold before experiencing these acute effects?

They have a higher threshold before experiencing these acute effects.

11

What is the main acute effect of alcohol consumption on the liver?

Fatty liver is a reversible condition in which fat droplets develop within the hepatocytes. This interferes with hepatocyte functioning and can cause low level inflammation.

12

what is the main acute effect of alcohol consumption on the stomach?

Acute gastritis is inflammation of the gastric mucosa, and causes sloughing (shedding) and haemorrhage of the mucosa.

13

What is the general effect of chronic alcohol metabolism?

The main effect is metabolic derangement, where fatty acid metabolism is increased significantly, resulting in fat deposition in the liver, kidneys, heart and muscle.

14

what are the risk factors for serious liver damage in heavy, chronic drinkers?

Infection with hepatitis C, polymorphisms in alcohol metabolism genes (cancer) and exposure to other hepatotoxins.

15

What is the structure of the functional units within the liver?

The hepatocytes are packed into little factories called 'lobules'. The lobules are a structured cluster of hepatocytes that filter blood that arrive from the branches of the portal vein and hepatic artery. After being filtered, the blood leaves the lobules via the hepatic vein.

16

What is the structure of the functional units within the liver?

The hepatocytes are packed into little factories called 'lobules'. The lobules are a structured cluster of hepatocytes that filter blood that arrive from the branches of the portal vein and hepatic artery. The blood reaches the hepatocytes via the sinusoids.

17

what are the names of the three metabolic pathways for alcohol in the body?

The main one is the cytochrome P450 pathway, followed by the alcohol dehydrogenase and catalase pathways.

18

Explain alcohol metabolism according to the cytochrome P450 pathway.

The cytochrome P450 pathway occurs in the microsomes of the smooth ER of liver cells (hepatocytes) . It involves the oxidation of ethanol by the enzyme CYP2E1, to produce water. It is converted into acetylaldehyde.

19

explain alcohol metabolism according to the alcohol dehydrogenase pathway.

Ethanol is oxidised by alcohol dehydrogenase to produce acetylaldehyde, in the cytosol of gastric mucosa cells. The concentration of alcohol dehydrogenase is larger in men than women.

20

explain the alcohol metabolism according to the catalase pathway.

Peroxisomes (like lysosomes) in the liver cells take ethanol and hydrogen peroxide and converts them into acetylaldehyde and water.

21

What byproduct of alcohol metabolism is responsible for the acute effects of ethanol oxidation?

Acetylaldehyde is responsible.

22

NADH is a byproduct of alcohol metabolism. What are the acute effects of excess NADH production?

Excess NADH over NAD production causes stimulation of lipid biosynthesis (fatty liver).

23

What byproduct does CYP2E1 from the cytochrome P450 pathway produce that is harmful?

ROS are produced by CYP2E1, and they can cause mitochondrial damage to the cells of the liver.

24

what are the acute effects of alcohol consumption on the brain?

It acts as a CNS depressant, and in particular depresses inhibitory control centres such as the limbic system (emotions-memory), the cerebellum (motor control) and the lower brain stem (BP and respiration).

25

Do chronic alcoholics have a higher or lower threshold before experiencing these acute effects?

They have a higher threshold before experiencing these acute effects.

26

What is the main acute effect of alcohol consumption on the liver?

Fatty liver is a reversible condition in which fat droplets develop within the hepatocytes. This interferes with hepatocyte functioning and can cause low level inflammation.

27

what is the main acute effect of alcohol consumption on the stomach?

Acute gastritis is inflammation of the gastric mucosa, and causes sloughing (shedding) and haemorrhage of the mucosa.

28

What is the general effect of chronic alcohol metabolism?

The main effect is metabolic derangement, where fatty acid metabolism is increased significantly, resulting in fat deposition in the liver, kidneys, heart and muscle.

29

what are the risk factors for serious liver damage in heavy, chronic drinkers?

Infection with hepatitis C, polymorphisms in alcohol metabolism genes (cancer) and exposure to other hepatotoxins.

30

What are the three diseases of the liver that make up the 'alcohol induced liver diseases'? What is the relationship between them?

There is cirrhosis, alcoholic hepatitis and steatosis. Chronic drinking can result in hepatitis, which is inflammation of the liver or in steatosis, which is fat accumulation in the liver. Repeated occurances of both will lead to cirrhosis (permanent scarring) of the liver.

31

What is the structure of the functional units within the liver?

The hepatocytes are packed into little factories called 'lobules'. The lobules are a structured cluster of hepatocytes that filter blood that arrive from the branches of the portal vein and hepatic artery. The blood reaches the hepatocytes via the sinusoids.

32

What would one see in a sample of a fatty liver?

Lumps of fat, or fatty deposits would be evident in the sample. This is due to increased fatty acid metabolism and decreased fatty acid oxidation by the mitochondria of the hepatocytes.

33

Describe the symptoms of alcohol hepatitis.

It occurs when the hepatocytes of the liver are permanently damaged by the metabolites of ethanol metabolism. An important antioxidant called glutathione is decreased in hepatitis, which means there is no protection from ROS's. It is the ROS's which cause necrosis of the hepatocytes and lead to inflammation, loss of liver function and neutrophil infiltration.

34

What are the symptoms of alcohol hepatitis?

fever, liver tenderness and jaundice.

35

Describe the symptoms of liver cirrhosis.

It is the most severe liver disease caused by chronic alcohol consumption. It is basically irreversible scarring of the liver, as the necrotic hepatocytes are replaced with fibrin. This leads to liver failure. It occurs as a result of continued necrosis, scarring, regeneration and inflammation.

36

What is the process behind liver cirrhosis?

Basically, liver steanosis (fatty liver) or hepatitis do not have to be precursors to cirrhosis. Acetylaldehyde build up forms complexes with protein that destroy the liver lobule structure. Excessive cytochrome P450 action produces high levels of ROS's which damage mitochondria.

37

What does the kuppfer cell do in regards to liver fibrosis?

Activated kuppfer cells cause increased cytokine secretion. Two of these, Platelet derived growth factor and tumor necrotic factor activate the stellate cells. This causes the stellate cells to multiply into fibroblasts that produce fibrin inside the spaces of the lobule, destroying its structure and killing the hepatocytes below it.

38

Name 3 other diseases due to chronic alcohol consumption

Foetal alcohol syndrome in unborn babies, acute pancreatitis and acute erosive gastritis in the stomach.