Liver And Alcohol Services

Question 1

Bilirubin metabolism

Answer 1

• a yellow bile pigment produced through the breakdown of red blood cells (haemolysis) prior to excretion through faeces and urine

Question 2

Jaundice

Answer 2

yellow discolouration of the sclera and/or skin in response to elevated bilirubin levels. Hepatic jaundice is caused by liver impairment- decreased ability of the liver to conjugate bilirubin, resulting in presence in conjugated and unconjugated bilirubin in the blood.

Question 3

Von gierke’s disease

Answer 3

most common, which is a deficiency in glucose-6-phosphatase. These patients present with lactic acidosis, hypoglycaemia, hyperuricaemia and hepatic enlargement.

Question 4

Glycogen metabolism

Answer 4

glycogenesis and glycogenolysis occur in the liver in order to maintain stable blood glucose levels
• Glycogen storage diseases are a variety of conditions caused by an absence/deficiency of the enzymes of glycogen metabolism. Generally speaking, these patients present with muscle cramps, hypoglycaemia and impaired physical development

Question 5

Lipid metabolism

Answer 5

lipolysis via beta-oxidation and ketogenesis
• Lipogenesis- Fatty acids are synthesised within the cytoplasm of hepatocytes, following maximal conversion of glucose to glycogen
• Ketosis is a build-up of ketone bodies in the blood. It can arise through a range of circumstances, including diabetic ketoacidosis (DKA), alcoholic ketoacidosis and starvation. Diabetic ketoacidosis occurs primarily in type 1 diabetics and can be the initial presenting complaint or a consequence of intercurrent illness.

Question 6

Protein metabolism

Answer 6

It stores more proteins than other tissues
• Can rapidly synthesise or degrade proteins.
• It also can quickly synthesise and degrade amino acids, unlike most other tissues.
• Amino acid synthesis via transamination
• Synthesis of clotting factors (prothrombin, Factor VII, IX, X and protein C)
• deamination and urea cycle

Question 7

Bleeding and the liver

Answer 7

the liver synthesises clotting factors for coagulation. Additionally, vitamin K-dependent clotting factors are particularly affected due to the decreased absorption of vitamin K that occurs in liver disease. As a result, patients might bruise easily and have a raised PT and INR

Question 8

Oedema and ascites

Answer 8

the liver synthesises almost all the body’s plasma proteins, without which the oncotic pressure of the blood falls, and fluid leaks out of the blood vessels into the extracellular space, leading to oedema. Additionally, cirrhosis increases resistance to the flow of blood which causes portal hypertension. The hypertension in the portal vein leads to yet more fluid leaking out of the portal vein contributing to ascites.

Question 9

GI bleeds

Answer 9

portal hypertension can also lead to varices (enlargement of the oesophageal veins) which can rupture and bleed. This is also coupled with an overall tendency to bleed due to diminished clotting factors.

Question 10

Fetor hepaticus (faecal/sweet-smelling breath)

Answer 10

this is a late sign and it thought to be due to thiols (sulphur-containing compounds) and to a lesser extent acetone on the breath. Thiols accumulate in the blood as portal vein hypertension leads to portosystemic shunting, meaning some thiols absorbed by the gut escape first pass metabolism. Raised acetone levels are due to an increase in fatty acid breakdown, as a response to impaired gluconeogenesis and glycogen storage.

Question 11

Symptoms of liver problems

Answer 11

• Build-up of fluid in the belly area (ascites).
• Jaundice
• Easy bruising.
• Itchy skin- excretion of bile
• Low blood pressure.
• Pain in the abdomen.
• Swelling in the legs or ankles.
• Tremors (shaking).
• Weakness, loss of balance or constant fatigue.
• Confusion or loss of orientation
• Pale coloured stool - less bile
• Dark urine- breakdown of erythrocytes and waste products

Question 12

Hepatic encephalopathy

Answer 12

damaged hepatocytes do not metabolise nitrogenous waste efficiently and some nitrogenous waste absorbed by the gut is shunted to the IVC due to portal vein hypertension. As a result, there are increased ammonia levels in the blood, and ammonia crosses the blood-brain barrier where it is metabolised by astrocytes to form glutamine. Glutamine increases the osmotic pressure in the brain, leading to brain oedema. A classic sign of hepatic encephalopathy, aside from the obvious confusion, agitation and vomiting, is asterixis (the liver flap).

Question 13

Storage of liver

Answer 13

• around 100g of glycogen is stored in the liver (400 kcal of energy)
• Lipid-solublevitamins A,D,E,K, are stored in the liver, as is Vitamin B12.
• Ironand copper minerals are stored in the liver.
• Glycogen storage diseases -Patients with an inherited deficiency in an enzyme involved in the glycogenolysis pathway may experience episodes of hypoglycaemia.Cori disease(glycogen debranching enzyme deficiency) andVon Gierke disease(glucose-6-phosphate enzyme deficiency) are types of glycogen storage diseases. Children may present with an enlarged liver, due to excessive glycogen storage.

Question 14

Detoxification

Answer 14

Detoxification:
• detoxifies alcohol
• Converts fat-soluble toxins into water-soluble form which can then be eliminated in urine

Question 15

Overview of functions of liver

Answer 15

Bilirubin metabolism
Glycogen metabolism
Lipid metabolism
Protein metabolism
Metabolic activation of vitamin D
Storage
Detoxification
Hormone production and elimination

Question 16

What does a liver blood test look for

Answer 16

• alanine aminotransferase (ALT) (0-45 IU/L) and aspartate aminotransferase (AST) (0-35 IU/L)- increased levels = liver damage
• Alkaline phosphotase (ALP) (30-120 IU/L)and gamma-Glutamyltransferase (GGT) (0-30 IU/L) - high levels = liver disease
• Bilirubin (2-17 umol/L) - high levels = liver disease
• Albumin (60-80 g/L) - low albumin = liver disease
• Prothrombin time (10.9 - 12.5s) - high PT = liver disease

Question 17

Common causes of elevated liver enzymes

Answer 17

• Over-the-counter pain medications, particularly acetaminophen (Tylenol, others)
• Certain prescription medications, including statin drugs used to control cholesterol
• Drinking alcohol
• Heart failure
• Hepatitis A
• Hepatitis B
• Hepatitis C
• Nonalcoholic fatty liver disease
• Obesity
• paracetamol overdose
• Herbal supplements

Question 18

Possible causes of elevated liver enzymes

Answer 18

• Alcoholic hepatitis (severe liver inflammation caused by excessive alcohol consumption)
• Autoimmune hepatitis (liver inflammation caused by an autoimmune disorder)
• Celiac disease (small intestine damage caused by gluten)
• Cytomegalovirus (CMV) infection
• Epstein-Barr virus
• Hemochromatosis (too much iron stored in your body)
• Liver cancer
• Mononucleosis
• Polymyositis (inflammatory disease that causes muscle weakness)

• Sepsis (an overwhelming bloodstream infection that uses up neutrophils faster than they can be produced)
• Thyroid conditions
• Toxic hepatitis (liver inflammation caused by drugs or toxins)
• Wilson’s disease (too much copper stored in your body)

Question 19

Risk factors for liver disease

Answer 19

• Heavy alcohol use
• Obesity
• Type 2 diabetes
• Tattoos or body piercings
• Injecting drugs using shared needles
• Blood transfusion before 1992
• Exposure to other people’s blood and body fluids
• Unprotected sex
• Exposure to certain chemicals or toxins
• Family history of liver disease

Question 20

Counsel a patient regarding alcohol use

Answer 20

1. Have a plan- use the Drink Free Days app to set a weekly unit target and stick to it
2. Switch from stronger stuff- Choose drinks that are lower in alcohol. Try lighter beers – under 4% ABV. As a rule of thumb, white and rosé wines are lower in strength than reds. Or try swapping some or all of your drinks for no or low-alcohol alternatives.
3. Stick with it - might take a bit of time to get used to the change from your usual choices, so if you notice a difference in taste with lower-strength drinks, do not give up! There are so many options, it’s likely there’s one out there for you – and switching means you can enjoy the health benefits of drinking less without losing your social life.
4. Shake up your social plans- Going for drinks is not the only way to see friends. You could watch a film, meet up for breakfast, grab a coffee and go for a walk, go bowling, head to the gym or sign up for a class to do together, for instance.
5. Set a booze budget - Sticking to a budgeted amount for alcohol can be a good way to drink less. If you are going out, try taking only the exact cash, or set up a spending alert on your card.
6. Write off the rounds- Being involved in rounds makes it easy to end up drinking more than you meant. Try to avoid them if you can, and do not feel like you have to say yes to a drink just because someone else is buying. There’s always next time.
7. Only wine and dine- Waiting for your evening meal before you have a drink – and having your first only once you’ve started eating – is another simple way to help you cut down.
8. Beat boredom- if a drink is a way you handle boredom or stress, try finding something else to do instead. Exercise is a great stress reliever, and simple things like cleaning, a new hobby or DIY can be a good way to occupy mind and body.
9. Stay hydrated- Have a glass of waterbefore youhave alcohol and alternate alcoholic drinks with water or other non-alcoholic drinks.
10. Take a break- Have several drink-free days each week.
11. Let them know- if you let your friends and family know you’re cutting down and it’s important to you, you could get support from them.

Question 21

Benefits of stopping drinking

Answer 21

• better mood, memory and quality of sleep
• save money
• Lower bp
• Lower cholesterol levels
• Lowers risk of stroke, hypertension, cancer, liver disease ‘

Question 22

Non-alcoholic fatty liver disease

Answer 22

term for a range of conditions caused by a build-up of fatin the liver (fat > 5-10% of liver’s weight). It’s usually seen in people who are overweight or obese.
Early-stage NAFLD does not usually cause any harm, but it can lead to serious liver damage, includingcirrhosis, if it gets worse.

Question 23

Stages of NAFLD

Answer 23

1 simple fatty liver (steatosis)- a largely harmless build-up of fat in the liver cells that may only be diagnosed during tests carried out for another reason. Benign and no liver damage
2 non-alcoholic steatohepatitis (NASH)- a more serious form of NAFLD, where the liver has become inflamed- estimated to affect up to 5% of the UK population
3 fibrosis - where persistent inflammationcauses scar tissue around the liver and nearbybloodvessels, but the liver is still able to function normally
4 cirrhosis- the most severe stage, occurring afteryears of inflammation, where the liver shrinks and becomes scarred and lumpy; this damage is permanent and canlead toliver failure andliver cancer

Question 24

Which stages of NAFLD are reversible

Answer 24

Stage 1