Liver Disease Flashcards
What are the main major functions of the liver?
- Metabolism and digestion
- Immunity
- Detoxification
- Storage of energy and nutrients
- Production of proteins, proteins in blood cells and signalling molecules/hormones
- First pass metabolism via portal vein
Describe the anatomy and physiology of the liver?
- Multi-lobed organ- 8 separate lobes- can function independently
- High capacity to regenerate as one or two lobes can be damaged
- Can constantly regenerate to deal with the toxic environment in its metabolic processes
- Most blood is provided by the portal vein from the GI tract
- Blood supply by the hepatic artery from the normal arterial route
- Hepatocytes regenerate quickly
- Each liver lobule has its own blood supply
Blood passes over the large surface area interior which has sinusoids - Blood in the centre of the liver lobule spreads blood out
- Bile is collected from the sinusoids which is released in the bile ducts, stored in gull bladder, then into the GI system
- Bile has roles in neutralising stomach acid and transport fatty acid
- Waste products are congragated in the bile, and then secreted in the urine and faeces
What are the numerous symptoms of liver disease?
- Jaundice- bilirubin build up (normally removed by bile)
- Ascites- build up of fluid outside abdomen (lack of albumin) causes loss of osmotic pressure (osmotic protein pressure)
- Puritis: skin itching
- Fat in faeces: inefficient bowel production
What are the liver function tests available to see if you have liver disease?
- Blood tests
- Liver enzymes and proteins (some may develop abnormal functions)
- Full medical check is required as some conditions and medication can affect liver
- Imaging
- Biopsy: take a liver cell and examine it in the lab
What are the standard liver function tests?
- ALT: alanine transaminase (common enzymes in liver)
- AST: aspartate transaminase
- Bilirubin: sign of jaundice
- Albumin
- Clotting time: prothrombin can be altered by Vitamin K absorption
- INR can also be measured
- GGT: high levels can mean liver damage
How is it possible that you can monitor alanine transaminase and aspartate transaminase for liver function tests in blood?
- When there’s damage to the liver, the hepatocytes release the two transaminases in blood stream
- Therefore, blood tests will show a high amount of it
- High amounts in drug induced, viral and auto immune hepatitis
Describe what bilirubin is?
- The breakdown product of haemoglobin
- Causes jaundice
- Levels in blood can mean liver disease
- Conjugation of bilirubin in the liver is a sign to see if the liver can cope with the amount it conjugates
Describe the liver function test of testing for albumin and the purpose of albumin?
- Synthesised in the liver for the purpose of oncotic pressure in RBC’s
- Albumin is important for transporting nutrients and drugs across
- Decrease can cause fluid retention and indicate liver disease
- Can occur also due to malnutration
Describe the liver function test for pro-thrombin?
- Time is measured to monitor the time taken for the blood to clot
- Longer it takes the reduction in clotting factors produced by the liver
- Vitamin K deficiency can lead to longer pro-thrombin time (malnutrition or block of bile)
- Represented by INR (international normalised ratio)
What can a liver biopsy do?
- A part of the liver is snipped off to check under a microscope
- Most reliable for checking liver damage
What is the purpose of imaging the liver? What does this show?
- It can show the size of the liver which can be an indication of liver damage
- Endoscopy can be done to check if any blockages in liver
Describe what acute liver disease is and give some examples of when this may occur?
- Self limiting episode that’s a sudden deterioration in patient
- History of disease thats less than 6 months
- Paracetamol overdose
- Viral infections
Describe what chronic liver disease and give some examples of when this may occur?
- Long term liver disease
- Examples:
- Non alcoholic fatty liver disease
- Alcoholic cirrhosis
- Damage due to viral infection
Define what cholestatic is and what it can lead to?
- When bile flow is reduced, blocked or impaired
- Elevated ALP, GGT, bilirubin, bile acids, cholesterol
- Lead to fibrosis
Define what hepatocellular is and what it can lead to?
- Damage to hepatocytes
- ALT and AST can be released by cells
- Serum levels may be elevated
- Fibrosis
What are the symptoms of severe liver disease?
- Fluid retention
- ascites
- portal hypertension (increase BP in portal vein)
- Jaundice
What are the three recognised stages of alcoholic liver disease?
- Stage 1: Alcoholic fatty liver disease
- Reversible by taking a break from drinking - Stage 2: Alcoholic hepatitis
- Chronic use over a long period of time
- Progression can be halted after stopping drinking - Stage 3: Cirrhosis
- Unlikely to survive unless you quit drinking permanently
How do you manage alcoholic liver disease?
- Quit drinking: Pharmaceutical interventions
- Diazepam used to treat alcohol withdrawal symptoms: can lead to seizures
- Deficiency in thiamine and malnutrition: IV and vitamin supplements
What is the difference between fatty liver disease and NASH (non alcoholic steato hepatitis)?
- Fatty liver disease: shows up as fat circular droplets under the microscope: occurs through drinking
- NASH: shows up as strains and lines of fat that have caused scarring: drink little or none at all- inflammation and pain
What is the treatment for non alcoholic fatty liver disease (NAFLD) and non alcoholic steatohepatitis (NASH)?
- No treatment options available
- Increase in exercise and improve diet
- Can treat the underlaying cause: diabetes, hypertension, excess cholesterol
- Avoid or reduce alcohol intake
What is hepatitis?
Inflammation of the liver
Describe the transmission of Hepatitis A, it’s symptoms and treatment?
- Transmission: Faecal oral route or sex/sharing needles
- Symptoms: initial vomiting, diarrhoea, nausea, malaise, mild fever
- Serious symptoms: jaundice, liver enlargement, skin itch/rash
- Treatment: self limiting (3 to 6 weeks)
- Vaccination is available
Describe the transmission of Hepatitis B, it’s symptoms, diagnosis and treatment?
- Transmission: transmitted from needles or tattooists, sex, mother to baby during birth
- Symptoms:
Similar to hepatitis A, symptoms show at 1-3 months, blood test needed for diagnosis - Treatment: Self limiting
- Progression to chronic hepatitis: may need anti-viral drugs
- Vaccination of high risk groups such as sex workers, drug injectors
Describe the transmission of Hepatitis C, it’s symptoms, diagnosis and treatment?
- Transmission: mainly via needles, rarely due to sex
- Symptoms:
- Asymptomatic until the development of chronic liver disease or cirrhosis - Diagnosis: only by blood test
- Anti-viral drugs that mainly inhibit viral replication
Describe paracetamol toxicity and what can it lead to?
- Leading cause of acute liver disease, often asymptomatic at the start, leads to nausea, vomiting, fatigue
- The liver cannot convert it to glucuronidation
- Therefore it’s converted to NAPQI
(toxic reactions to proteins and metals)
How do you treat paracetamol poisoning?
- 24 hours of overdose - irreversible damage
- Liver failure 48 to 96 hours after
- Within 1 hour: charcoal treatment will absorb paracetamol
- ACETYLCYESTEINE: IV treatment after, stagger dose (more than necessary)
- Refer to national poison service if more than 24 hours
Describe what must be done in prescribing if a patient is suffering from hepatic impairment?
- Prescribing kept to a minimum as the liver is responsible for metabolising and duration of action of drugs
- If a drug is considered hepatotoxic, you may have to change the concentration of the drug and the dose
Describe what can occur in hepatic blood flow when you have liver disease? And how this also may affect drugs?
- Hepatic blood flow can be decreased with liver disease
- Bioavailability in first pass metabolism is increased
- Drugs that have high extraction rate due to bioavailability, need to have strength reduced by 10 to 50%
- Portosystemic: Blood can be diverged away from the liver due to disease
Describe what can occur in hypoproteinaemia when you have liver disease? And how this also may affect drugs?
- Low serum albumin: main site of drug binding in plasma
- Leads to increased concentration of free drugs in body
- This can lead to problems with warfarin or phenytoin that really rely on this
- Reduced clotting factors- increased sensitivity to anti-coagulant
- Increased fluid retention
- NSAIDS to be avoided as can cause fluid retention
