Alcohol, Liver Disease And Nutrition Flashcards
How have drinking habits in the UK changed over time? (Adults and 11-15 year olds)
Dropped by ~2 litres/adults per year in 10 years
In 11-15 year olds prevalence of drinking has also dropped to 38%
Also drinking much more wine than previously
Structure of the liver and what happens during cirrhosis
- blood comes in via artery or the portal vein
- blood drains out of central vein and sinusoids
- hepatocytes are organised into lobules
- during cirrhosis have fibrosis, then bridging, and scar tissues tighten to get nodule formation
Symptoms of liver disease
- tiredness
- repeated infections
- irritability
- lack of concentration
- impotence, menstrual disturbance
Risk factors for liver disease
- excessive alcohol consumption (which can exacerbate liver disease progression in the following)
- viral hepatitis
- obesity, high cholesterol, diabetes, heart disease
- family history of liver disease
- multiple drugs
Alcohol related hospital admissions: age groups most likely, why were they admitted?
- most likely age group for hospital admission: 44% between 55-74
- nearly half of all admissions were due to CVD, 19% for mental and behavioural disorders due to alcohol
Binge drinking: definition, trends over time, geography where incidence is highest
- drinking more than twice your DAILY recommended amount in one sitting i.e >4 units a day
- public health messages are working and the incidence of binge drinking has declined
- binge drinking is greatest in North of England and in more socially deprived areas
What had happened to affordability of alcohol over time?
- affordability of alcohol has increased over time, so people can drink more
- as a result, household expenditure on alcohol has gone up
- in scotland, introduced minimum unit pricing for alcohol which shot prices up. Reduced alcohol expenditure in the 5% of the population whom are doing most of the drinking
Populations who are drinking the most
- age: 44-65 and over (more expendable income?) but more habitual drinking i.e drink everyday
- those in professional/managerial occupations
- those with higher degrees
Alcohol related mortality
The lowest socioeconomic class are disproportionately affected by alcohol-related mortality, they actually drink less than those with higher degrees/ professional occupations but have higher mortality
Unlike in other diseases, mortality due to liver related diseases has increased over time
Alcoholic liver disease accounts for 2/3 of alcohol-related deaths
Drink driving casualties have also reduced over time
Recommended alcohol limits in the UK (NHS)
- 14 units per person/week
- NHS recommends several alcohol-free days each week
Binge drinking
- drinking more than a daily allowance (4 units) on 1 day
- relative risk of liver disease increases exponentially after 10 units per week
- binge drinking weakens the junctions in intestines, causing more bacterial endotoxins to leak through
The liver-gut relationship
- dysfunctional liver leads to intestinal permeability due to increased blood pressure from the portal vein
- nutritional factors, associated digestive disorders, hormonal factors, alcohol, diabetes and bile salts can all also contribute to increased intestinal permeability
- this leads to gut microbiome changes too
- endotoxins and bacteria released from increased intestinal permeability can also feedback to the liver by causing systemic inflammation (WBC and inflammatory response), which can also contribute to neuroinflammation
What is the damage caused by alcohol?
- in hepatocytes: alcohol dehydrogenase converts ethanol to acetaldehyde, and acetaldehyde dehydrogenase converts to acetate, which would be converted to acetyl CoA to acetyl CoA synthase (which can produce fat, citric acid cycle, pyruvate)
- CYP2E1 is a enzyme which generates NAD for the first oxidation and is up regulated in alcohol excess but the acetaldehyde dehydrogenase is not, meaning the aldehyde accumulates (which contributes to ROS and damage DNA). At low concentrations it is easily metabolised, mutations in ALDH leads to flushing
- up-regulation of CYP2E1 generates ROS and reduces antioxidants
- Fe stores increase which raises ROS, as Fe is up-regulated during cellular damage
- mitochondria decrease
- kupffer cells (which get rid of bacterial endotoxins), increase ROS and TNFa
- these increase stellate cells produce scar tissue (collagen) which contributes to fibrosis
Actions of CYP2E1
- SNPs affect enzyme activity and is inducible by chronic ethanol ingestion
- increased activity increases ROS
- ## decreases retinoic acid or retinol in tissues which have important roles in cell growth
Effects of alcohol in the liver
1) oxidative stress
2) reduction in antioxidant levels eg glutathione
3) dysregulation of Fe transport increase hepatic stores
4) depletion of hepatic mitochondria
5) lipid deposition
6) DNA damage
7) release of pro-inflammatory cytokines
8) necrotic cell death of hepatocytes
9) stellate cell activation
10) white cell infiltration: amplification of inflammation
