Liver Disease Flashcards
Main functions of the liver
Central to maintenance of homeostasis Storage Clearance Filtration Secretion Excretion Synthesis Metabolism
Methods of detoxification
Destroys endogenous and exogenous substances Destroys cellular debris Deamination of amino acids Removal of bilirubin Hormone deactivation
Features of acute liver disease
Less than six months duration
Often resolves spontaneously, self limiting
Rapid decline in liver function
May be asymptomatic
100% association with encephalopathy and coagulopathy
Can result in acute liver failure
Features of chronic liver disease
Over six months duration Often symptomatic Secondary to long-standing cell damage Permanent structural change Loss of normal liver architecture Cirrhosis- fibrous scars, divides the liver into nodules
Causes of liver disease
Viral infection- Hepatitis A-E Alcohol Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Cholestasis (intra-hepatic, extra-hepatic) Immune disorders Vascular abnormalities Metabolic disorders Genetic disorders
Features of viral infection
Hep A- faecal contamination of food or drink
Hep B- blood/blood contamination
Hep C- blood/blood contamination
Hep D- have to have Hep B to get Hep D
Hep E- faecal contamination of food or drink
Causes of liver disease- alcohol features
Single most significant cause of liver disease in the Western World
Eventually leads to cirrhosis
Fibrous tissue in liver increases resistance to blood flow from the portal system resulting in portal hypertension
As liver cell death continues, leads to liver failure
Rate of progression (and regression) linked to further alcohol consumption
Drug related liver disease- type A
Dose related
Withdrawal of precipitating drug results in reversal
e.g. paracetamol, tetracyclines, methotrexate
Drug related liver disease- type B
Idiosyncratic (related to a drug property)
Hypersensitivity or metabolic
Symptoms of liver disease
Non specific symptoms- weakness, fatigue, general malaise
Poor nutrition status- weight loss, anorexia, loss of muscle bulk
Abdominal discomfort/ pain
Tenderness over liver
Jaundice
Cutaneous symptoms of liver disease
Hyperpigmentation
Scratch marks
Spider naevi
Non-specific- palmar erythema, Dupuytren’s contracture, finger clubbing
Abdominal signs of liver disease
Distension
Hepatomegaly (increase in liver size)
Splenomegaly (increase in splen size)
Umbilical and paraumbilical veins
Jaundice
Does not automatically mean liver disease Yellowing of skin and sclerae Hepatocellular- drugs, hepatitis, tumour Cholestatic- obstruction Prehepatic- increased blood breakdown
Pruritis
Deposition of bile salts in the skin
Concentration does not correlate with severity
Most debilitating in cholestatic conditions
Obstruction relieved by endoscopy, radiology, surgery
Pharmacological treatment favoured for other causes
Portal hypertension
Increase pressure in portal venous system leads to collateral vein formation and shunting of blood to systemic circulation
Contributes to formation of ascites and development of encephalopathy
Complications- variceal bleed
Ascites
Accumulation of fluid within the abdominal cavity
Caused by central hypovolaemia, reduced serum albumin, portal hypertension and splanchnic artery vasodilation
Clotting abnormalities
Hepatocyte failure causes defective synthesis of clotting factors I and V, leading to increased tendency to bleed
Also leads to defective bile salt excretion, malabsorption of vitamin K and defective synthesis of II, VII, IX and X
Sexual characteristics
Endocrine changes most common in alcoholic liver disease
Thought to be due to poor metabolism of oestrogen
Males- testicular atrophy, female body hair, gynaecomastia
Females- menstrual irregularity, reduced fertility
Biochemical investigations
Simple, inexpensive, easy to perform Useful to monitor disease progression or response to therapy Enzymes- hepatocellular or cholestatic Bilirubin Synthetic function- clotting time
Other investigations
Laboratory investigations- Hep A, B and C virology, immunoglobulins, lipid profile etc.
Imaging- ultrasound- preliminary assessment; CT and MRI- precise definition of abnormalities
Biopsy- gold standard for establishing diagnosis and assessing severity
Treatment of pruritis
Anion exchange resins e.g. colestyramine, colestipol- bind bile acids and prevent reabsorption, side effects: GI, fat and vitamin malabsorption, poor adherence due to palatability
Counselling- take interacting drugs one hour before or four hours after colestyramine, benefits may take up to one week to become apparent
Antihistamines
Arsodeoxycholic acid
Topical therapies e.g. calamine lotion
Treatment of ascites
Aim is to mobilise intra-abdominal fluid
Simple measures include reducing sodium intake and fluid restriction
Moderate to severe ascites requires diuresis or paracentisis (using needle to pull blood out)
Pharmacological treatment of ascites
Diuretics
Spironolactone is first line agent- blocks sodium reabsorption in kidney tubules, 50-400mg daily, titrate slowly, causes gynaecomastia and hyperkalaemia, add furosemide if severe, acre to avoid excessive diuresis
Paracentisis
Used in refractory ascites, combined with albumin administration, does not affect mechanisms responsible for fluid accumulation, repeated every 2-4 weeks in outpatient setting
TIPS
Transjugular Intrahepatic Portosystemic Shunt
Prevents recurrence in refractory ascites, shunt stenosis is common, bypasses liver to reduce pressure on circulation
Treatment of encephalopathy
Reversible neuropsychiatric condition- lack of awareness, altered mental state, disorientation, coma
Complex aetiology- portosystemic shunting, metabolic dysfunction, alteration of BBB, ammonia heavily implicated
Precipitated by GI bleeding, spontaneous bacterial peritonitis, drugs- remove if present
Pharmacological treatment of encephalopathy
Lactulose- acidifies colonic contents, leading to ionisation of nitrogenous products and therefore reduction in absorption, 30-40ml/day titrated to achieve 2-3 soft stools per day, causes bloating and diarrhoea
Antibiotics- metronidazole reduces ammonia production by GI bacteria
Treatment of clotting abnormality
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 Also avoid NSAIDs, aspirin and anti-coagulants
Treatment of varices
Shunting of portal blood to systemic circulation- pre-existing vessels dilate, active angiogenesis
Initial treatment- stop immediate bleeding, treat hypovolaemic shock, aim to prevent recurrent bleeding
Immediate treatment of varices
Terlipressin (vasopressin analogue): systemic vasoconstrictor, infused for 2-5 days
Prevention of varices
Band ligation: long term non-selective B blockers e.g. propanolol, decrease PHT by splanchnic vasoconstriction and decrease portal blood flow
Acute Liver Failure
Rapid deterioration in liver function in a previously healthy individual, most common cause is a paracetamol overdose
Complicated to manage: CNS, CV and renal systems affected, infection and bleeding can be life threatening
Paracetamol and the liver
Most common agent of intentional self harm, 20-30 tablets consumed within 24 hours can result in severe hepatocellular necrosis
Saturation of glutathione pathway
Paracetamol toxicity
0-24 hours: asymptomatic or non-specific signs
24-48 hours: RUQ pain, jaundice, deranged bloods
>72 hours: jaundice, somnolence, liver failure
Results in: cerebral oedema, shock, sepsis, renal failure
Prescribing considerations
Impaired drug metabolism- main route of elimination for many drugs, liver disease must be severe for clinically relevant changes to occur, care with rifampicin and fusidic acid
Hypoproteinaemia- albumin produced in the liver, affects highly protein bound drugs
Impaired clotting- clotting factors synthesised in the liver, increased sensitivity to oral anticoagulants
Hepatic encephalopathy- many drugs can impair cerebral function, care with sedative drugs, opioids, diuretics that decrease K+
