~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.
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.
Toxic effects of alcohol are mediated either by the direct effect of alcohol itself, or through the effects of alcohol ______.
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____.
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 (1st step of its metabolism), individuals who drink heavily are at a ____2____ risk of paracetamol toxicity.
What is a normogram used for?
To determine whether someone needs an antidote for paracetamol poisoning or not.
Where is the damage to the liver caused by CYP2E1 induction the greatest?
CYP2E1 causes the most damage to the areas of the liver with the lowest oxygen levels.
State the 2 aspects of the chronic effects of alcohol.
- 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.
What is the diagnosable difference between NAFLD and ALD?
Whether the patient states they are a heavy drinker or not.
(The differences are indistiguishable down a microscope).
What is the best treatment for ALT?
In the UK, how long does a patient have to abstinent for before they qualify for a lover transplant?
- 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)
Alcohol is directly toxic to ______ in the gut and can therefore reduce the ability to absorb nutrients.
What is the first manifestation of ALD?
Fat build-up within the liver cells.
Stellate cells normally store Vitamin _1_ but when they become activated they contract and lay down collagen and ____2____ tissue within the liver.
A chronic disease of the liver marked by degeneration of cells, inflammation, and fibrous thickening of tissue.
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____
Define compensated cirrhosis.
Liver is scarred but there remain enough hepatocytes to keep the liver functioning sufficiently.
Liver is no longer clearing the toxins from the blood effectively. This effects the brain and can cause confusion.
What is Asterixis?
An asymmetrical jerking tremor, unlike the fine tremor caused by kidney failure.
Define portal hypertension.
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.
What happens in hepato-renal syndrome?
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.
What medicines are there for treating NAFLD and ALD?
There are none.
~__% of pancreatitis is caused by high alcohol consumption.
Inflammation of the pancreas
Define first pass metabolism.
A phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation.
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.
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.
Potential therapies for ALD