Lecture 3- alcohol induced injury

Question 1

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

Answer 1

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.

Question 2

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

Answer 2

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

Question 3

Explain alcohol metabolism according to the cytochrome P450 pathway.

Answer 3

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.

Question 4

explain alcohol metabolism according to the alcohol dehydrogenase pathway.

Answer 4

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.

Question 5

explain the alcohol metabolism according to the catalase pathway.

Answer 5

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

Question 6

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

Answer 6

Acetylaldehyde is responsible.

Question 7

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

Answer 7

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

Question 8

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

Answer 8

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

Question 9

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

Answer 9

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).

Question 10

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

Answer 10

They have a higher threshold before experiencing these acute effects.

Question 11

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

Answer 11

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.

Question 12

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

Answer 12

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

Question 13

What is the general effect of chronic alcohol metabolism?

Answer 13

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

Question 14

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

Answer 14

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

Question 15

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

Answer 15

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.

Question 16

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

Answer 16

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.

Question 17

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

Answer 17

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

Question 18

Explain alcohol metabolism according to the cytochrome P450 pathway.

Answer 18

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.

Question 19

explain alcohol metabolism according to the alcohol dehydrogenase pathway.

Answer 19

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.

Question 20

explain the alcohol metabolism according to the catalase pathway.

Answer 20

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

Question 21

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

Answer 21

Acetylaldehyde is responsible.

Question 22

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

Answer 22

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

Question 23

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

Answer 23

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

Question 24

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

Answer 24

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).

Question 25

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

Answer 25

They have a higher threshold before experiencing these acute effects.

Question 26

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

Answer 26

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.

Question 27

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

Answer 27

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

Question 28

What is the general effect of chronic alcohol metabolism?

Answer 28

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

Question 29

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

Answer 29

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

Question 30

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

Answer 30

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.

Question 31

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

Answer 31

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.

Question 32

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

Answer 32

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.

Question 33

Describe the symptoms of alcohol hepatitis.

Answer 33

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.

Question 34

What are the symptoms of alcohol hepatitis?

Answer 34

fever, liver tenderness and jaundice.

Question 35

Describe the symptoms of liver cirrhosis.

Answer 35

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.

Question 36

What is the process behind liver cirrhosis?

Answer 36

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.

Question 37

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

Answer 37

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.

Question 38

Name 3 other diseases due to chronic alcohol consumption

Answer 38

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