Unit 4 - The Liver 2 Flashcards
What sexual characteristics are affected by liver disease?
Endocrine changes most common in alcoholic liver disease
- poor metabolism of oestrogen
How are males affected by liver disease?
Testicular atrophy
Female body hair
Gynaecomastia
- increased breast tissue
How are females affected by liver disease?
Menstrual irregularity
Reduced fertility
How can liver disease be tested biochemically?
Simple, inexpensive, easy to perform Useful to monitor disease progression or response to therapy Enzymes - hepatocellular - AST - ALT Bilirubin Synthetic function - PT and INR - albumin
Apart from biochemical liver tests, how else can liver disease be investigated?
Laboratory investigations - hepatitis A - hepatitis B - hepatitis C - immunoglobulins - lipid profile Imaging - ultrasound - preliminary assessment - CT and MRI - precise definition of abnormalities Biopsy - gold standard for establishing diagnosis and assessing severity
What is the treatment for pruritis?
Anion exchange resins
- bind bile acids and prevent reabsorption
What are the side effects of anion exchange resins?
GI issues - constipation - diarrhoea - flatulance Fat and vitamin malabsorption
Why is the poor adherence of anion exchange resins?
Poor palatability
What counselling points should be given for treating pruritis?
Take interacting drugs 1 hour before or 4 hours after colestyramine
Benefits may take up to one week to become apparent
Give two examples of anion exchange resins used to treat pruritis
Colestyamine
Colestipol
Apart from anion exchange resins, what else can be used to treat pruritis?
Antihistamines - sedating properties useful if pruritis affects sleep Ursodeoxycholic acid - treats cholestatic disease Rifampicin - inhibits hepatocyte uptake of bile salts - decreases reabsorption Opiod antagonists - itching due to increased endogenous opiate tone Topical therapies - calamine lotion menthol 2% in aqueous cream
What is the aim of treating ascites?
Mobilise intra-abdominal fluid
What non-pharmacological treatments are there for ascites?
Simple measures: - reduce sodium intake - fluid restriction Moderate to severe measures - diuresis (increase urine output) - paracentesis (sucked out with a needle)
What pharmacological treatments are there for ascites?
Diuretics
- increase diuresis
Spironalactone is first line agent
- blocks sodium reabsorption in kidney tubules
- dose range 50 - 400 mg daily
- titrate slowly
- side effects
- gynaecomastia (potassium sparing diuretic)
- hyperkalaemia (potassium sparing diruetic)
Add furosemide if severe
Care to avoid excessive diuresis
How is paracentesis used to treat ascites?
Use in refractory ascites
Combined with albumin administration
Does not affect mechanisms responsible for fluid accumulation
- transient effect
Repeated every 2 - 4 weeks in outpatient setting
What is TIPS?
Transjugular Intrahepatic Portosystemic Shunt
Where is the shunt placed in TIPS?
What is a shunt ?
Between hepatic portal vein and systemic circulation
In medicine, a shunt is a hole or a small passage which moves, or allows movement of, fluid from one part of the body to another
What are the drawbacks of TIPS?
Prevents recurrence in refractory ascites
Shunt stenosis is common
What percentage of patients with cirrhosis develop encephalopathy?
40%
More than half die within a year
What are the symptoms of encephalopathy caused by cirrhosis?
Reversible neuropsychiatric condition
- lack of awareness
- altered mental state
- disorientation
What are the causes of encephalopathy in cirrhosis?
Portosystemic shunting Metabolic dysfunction Alteration of Blood Brain Barrier Ammonia heavily implicated - accumulation in CNS
What is encephalopathy precipitated by?
GI bleeding
Spontaneous Bacterial Peritonitis (SBP)
Drugs
What is the treatment for encephalopathy?
Lactulose
Antibiotics
How is lactulose used to treat encephalopathy?
Acidifies colonic contents
- leading to ionisation of nitrogenous products and therefore a reduction in absorption
30 - 40 ml/day titrated to achieve 2 - 3 soft stools per day
Side effects
- bloating
- diarrhoea
How are antibiotics used to treat encephalopathy?
Metronidazole reduces ammonia production by GI bacteria
What is used to treat clotting abnormality caused by liver disease?
Phytomenadione IV (vitamin K)
- 10mg daily for 3 days
- oral not as effective as IV (therefore not used)
Not effective in patients with significant disease
What medications should patients with a clotting abnormality avoid?
NSAIDs
Aspirin
Anticoagulants
What are varices?
Development of weak and leaky vessels
What is the treatment for varices?
Shunting of portal blood to systemic circulation
- pre-existing vessels dilate
- active angiogenesis
What is the initial treatment for varices?
Stop immediate bleeding
Treat hypovolaemic shock
- increase blood volume
Aim to prevent recurrent bleeding
What medication should be given immediately to treat varices?
Terlipressin (vasopressin analogue)
- systemic vasoconstrictor
- infused for 2 - 5 days
How can varices be prevented?
Band ligation Long term non-selective beta-blockers - propanolol - reduced portal hypertension by splenic vasoconstriction - reduced portal blood flow
What is Acute Liver Failure (ALF)?
Rapid deterioration in liver function in a previously healthy individual
What is the most common cause for Acute Liver Failure in the UK?
Paracetamol overdose
Why is Acute Liver Failure complicated to manage?
Multiple organ systems affected - central nervous system - cardiovascular - renal systems affected Infection and bleeding can be life threatening
How many paracetamol tablets consumed within 24 hours can result in severe harm?
20 - 30 tablets
Why is paracetamol overdose hard to metabolise?
Saturation of glutathione pathway
Which chemical is produced in the metabolism of paracetamol when glutathione is exhausted?
NAPQI
When does NAPQI cause necrosis of liver and kidney?
When glutathione reserves are less than 30%
What is the timeline after paracetamol overdose?
0 - 24 hours - asymptomatic - non-specific signs 24 - 48 hours - right upper quadrant pain - jaundice - deranged bloods - coagulopathy > 72 hours - jaundice - somnolence - liver failure
What is the result of paracetamol overdose?
Cerebral oedema
Shock
Sepsis
Renal failure
What is the treatment for paracetamol overdose in the first 4 hours?
Activated charcoal
- mop up GI tract
Do not treat with N-ac
- wait for paracetamol to be absorbed into the blood to find single paracetamol concentration related to time of ingestion
What is the treatment for paracetamol overdose between 4 and 36 hours after ingestion?
N-actylcysteine
- almost 100% effective if given within 8 hours
- increases glutathione concentration
When was legislation introduced to restrict the sale of paracetamol?
1998
- pack size
- packaging
What was the effect of restricting the sale of paracetamol?
Significant decrease in paracetamol overdose
- Heath hospital still admits 1 patient a week
Why do prescribers need to be aware of liver disease in patients?
Impaired drug metabolism
- main route of elimination for many drugs
- hepatic reserve is large
- liver disease must be severe for clinically relevant changes occur
- care with rifampicin and fusidic acid
What is hypoproteinaemia?
Low levels of protein in the blood
- albumin
What are the implications of hypoproteinaemia?
Albumin is produced in the liver Affects highly protein bound drugs - low albumin - less albumin binding - increased free drug concentration - exposure to drug increased
What prescribing considerations are there in patients with liver disease?
Impaired clotting - clotting factors synthesised in liver - increased sensitivity to oral anticoagulants Hepatic encephalopathy - many drugs can impair cerebral function - lower awareness - care with - sedative drugs - opioids - diuretics that reduce potassium levels Fluid overload - oedema/ascites exacerbated by drugs that cause fluid retention - NSAIDs - corticosteroids Hepatotoxic drugs - dose related or idiosyncratic - avoid - use with extreme caution
