Liver Disease - 2

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  • Created by: LBCW0502
  • Created on: 30-11-19 13:10
What are the causes of liver disease? (1)
Alcohol, viral infections (hep A/B/C), inherited and metabolic disorders (Wilson's disease, glycogen storage disease). Immune disease of liver (autoimmune hepatitis, PBC, PSC). Vascular abnormalities (Budd-Chiari syndrome, Veno-Occulusive disease)
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What are the causes of liver disease? (2)
NAFLD, drugs and toxins, cancer, biliary tract disorders, infections, other
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Alcohol is a factor in which medical conditions?
Factors in more than 60 medical conditions including - mouth, throat, stomach, liver cancer, high BP, cirrhosis of liver, depression. Binge drinking also can issue
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What are the government recommendations regarding alcohol intake for men and women?
14 units per week (with 2-3 days free of drinking)
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Give examples of effects of alcohol on the body (1)
Headaches, blackouts, impaired judgement, degeneration of NS, risk of haemorrhage (pressure on portal circulation), corrosive effect on gullet, risk of cancer, muscle weakness, cirrhosis, weaken heart, high BP, peptic ulcer, malnutrition, pins/needle
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Give examples of effects of alcohol on the body (2)
Inflammation of intestines, tremors, men - depressed testicular production, breast growth due to female hormones not broken down by liver, women - failure to ovulate, spontaneous abortion
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What are the short term effects of alcohol on the body?
Anxiety, decreased RR, GI disturbances, impaired judgement, loss of consciousness, importance, acute poisoning, complexion/effect on appearance, unintentional injuries
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What are the long term effects of alcohol on the body?
Liver disease, cancer (several types), pancreatitis, GI ulceration, osteoporosis, infertility, heart disease, stroke, increased BP, obesity, dementia
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What are the stages of liver disease?
Healthy liver - fatty liver (deposits of fat lead to liver enlargement) - liver fibrosis (scar tissue forms) - cirrhosis (growth of connective tissue destroys liver cells)
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Describe the metabolism of alcohol (1)
Oxidation to acetylaldehyde by alcohol dehydrogenase. Acetaldehyde is thought to be the most important metabolite leading to liver damage.
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Describe the metabolism of alcohol (2)
Aldehyde dehydrogenase metabolises acetylaldehyde to acetate which is further metabolised to water, fatty acids and CO2.
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What is the effect of high alcohol intake on liver metabolism?
Increase in microsomal ethanol oxidising system (CYP450 2E1). Metabolises alcohol to unstable free radicals
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Describe features of a fatty liver (steatosis) - 1
Accumulation of fat in liver. May occur after only a few days. Rarely symptomatic. Reversible with abstinence. Disruption of metabolic pathways (NADH redox imbalance) in liver cause accumulation large droplets lipid within hepatocytes
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Describe features of a fatty liver (steatosis) - 2
Usually only has minimal effect on liver function. Fat deposits in liver can occur a few days after drinking alcohol
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Describe features of steatohepatitis (acute alcoholic hepatitis) - 1
Accumulation of fat plus hepatocellular injury (inflammation and fibrosis). Pathogenesis poorly understood which can make treatment difficult. 4 mechanisms of injury (oxidative stress, acetaldehyde accumulation, altered protein function
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Describe features of steatohepatitis (acute alcoholic hepatitis) - 2
Severity can range from mild to severe liver dysfunction. Usually improves with abstinence although proportion patients will develop cirrhosis despite abstinence
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Describe features of steatohepatitis (acute alcoholic hepatitis) - 3
Liver appears yellow, inflammation, lots of fat in liver, lose functionality (can improve if patient stops drinking alcohol – get rid of fat in liver)
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Describe features of fibrosis/cirrhosis (1)
Inflammation - fibrinogenesis + collagen deposition. Mechanism activation unclear but thought to include direct injury by free radicals plus expression inflammatory cytokines
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Describe features of fibrosis/cirrhosis (2)
Patient may exhibit signs of decompensation including encephalopathy, ascites, coagulopathy. Proportion of patients will develop HCC. Abstinence key to management
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Why doesn't everyone with high alcohol intake get liver damage?
Intake (threshold), consumption patterns, dependency, genetics, gender, BMI, race, environmental influences e.g. chronic viral disease
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Outline the management plan for acute alcoholic hepatitis on a background of chronic liver disease (1)
Initially withdrawal symptoms will need to be managed (including management of seizures). Manage malnutrition/vitamin deficiency to prevent complications. Treat acute alcoholic hepatitis using drugs targeting inflammatory component
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Outline the management plan for acute alcoholic hepatitis on a background of chronic liver disease (2)
Manage other complications related to alcohol use e.g. pancreatitis. Manage complications of liver disease e.g. cirrhosis, HE, coagulopathy, ascites. Abstinence - key for all patients
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Outline the management plan for acute alcoholic hepatitis on a background of chronic liver disease (3)
Primary vs secondary detox. Symptoms can range from mild to severe - marked tremor, fear/delusions, restlessness/agitation, fever, rapid pulse, dehydration, seizures, delirium tremens
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Outline the management plan for acute alcoholic hepatitis on a background of chronic liver disease (4)
Treated with combination of sedatives and vitamin supplementation - chlordiazepoxide and pabrinex. Alcohol withdrawal protocol (diagram)
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Describe features of benzodiazepines (1)
Chlordiazepoxide - long t1/2, sedative and anti-convulsant properties, slower onset action, low dependence forming potential. Chlormethiazole was traditionally used – respiratory depression, addiction/dependence
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Describe features of benzodiazepines (2)
BDZs can be given as - front loading-loading dose followed by repeat dosing every 90 mins - light sedation, symptom triggered dosing, tapering dose regimen. Shorter acting e.g. oxazepam or lorazepam, more suitable in patients with hepatic impairment
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Describe features of benzodiazepines (3)
Most BDZs are highly lipophilic and undergo extensive liver metabolism - cirrhosis. Most form active metabolites. Diazepam metabolism reduced in patients with hepatic impairment (reduce dose)
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Describe features of benzodiazepines (4)
Variation - many use lorazepam or oxazepam but as shorter acting, risk seizures, t1/2 altered in presence of hepatic dysfunction, no active metabolites
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Describe features of pabrinex (1)
Vitamin deficient due to poor diet (high in carbohydrate, low in protein, vitamins and minerals). Malabsorption in intestinal mucosa. Thiamine deficiency - polyneuritis with motor and sensory defects
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Describe features of pabrinex (2)
Wernike's encephalopathy (opthlamoplegia, nystagmus, ataxia, learning and memory impaired, 10-20% mortality). Korsakoff's - permanent
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Describe features of pabrinex (3)
1 pair = thiamine 250 mg, ascorbic acid 500 mg, nicotinamide 160 mg, pyridoxine 50 mg, riboflavin 4 mg. Dose 1-3 pairs BD-TDS. IM preparation is available - not if coagulopathic
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Describe features of pabrinex (4)
IV infusion in 50-100mL NaCl 0.9% or Dex 5% over 30 mins (allergic reactions if bolus). Treatment - vit B and thiamine
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Describe features of acute alcoholic hepatitis (1)
Clinical syndrome of jaundice and liver failure. May be reversible if stop drinking but many patients may also have underlying cirrhosis. Can also occur several weeks after the patient has stopped drinking. Typical age at presentation - 40-60 yrs
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Describe features of acute alcoholic hepatitis (2)
Characterised by fever, hepatomegaly, leukocytosis and clinical/lab signs of liver failure (ascites). Raised AST, WCC, neutrophil count, bilirubin and INR. Raised creatinine (hepato-renal syndrome). Hospitalised patients - 50%, scoring system MELD
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What is the pharmacological management for acute alcoholic hepatitis? (1)
Corticosteroids - most effective. Prednisolone 40-60mg OD for 5-7 days. Aim to switch off inflammatory process. Problems include increased risk infection and GI bleeding. Mortality on treatment can be high
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What is the pharmacological management for acute alcoholic hepatitis? (2)
Pentoxifylline (Oxypentifylline). Non-selective PDE inhibitor which inhibits TNFa (pro-inflammatory cytokine). 400 mg TDS for 28 days
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What is the pharmacological management for acute alcoholic hepatitis? (3)
Other anti TNF agents - infliximab, entanercept. Antioxidants - Vit E, silymarin (milk thistle), Co Q10, trace elements. Propylthiouracil - reduce O2 consumption in hepatocyte. Enteral feeding. MARS. Colchicine - inhibit collagen synthesis
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What is the pharmacological management for acute alcoholic hepatitis? (4)
None of the agents have shown significant benefit and many are associated with significant adverse effects
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What is the management for alcoholic cirrhosis? (1)
Treat episodes of decompensation and minimise risk complications. Other pharmacological management - diuretics (ascites), propranolol (portal hypertension), vitamin K (coagulopathy), antibiotics (SBP). Lactulose for HE (precipitants)
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What is the management for alcoholic cirrhosis? (2)
Transplant (candidate - abstinent from alcohol for at least 6 months)
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Describe features of dependence and withdrawal (1)
Alcohol affects glutamine, GABA, dopamine, endogenous opioid systems. Alcohol consumptions linked with beta endorphin release, stimulate DA release, pleasurable feelings. Alcohol facilitates GABA transmission (inhibition)
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Describe features of dependence and withdrawal (2)
Chronic alcohol intake - reduce number of GABA receptors to counteract alcohol-induced increase in GABA activity. Alcohol inhibits excitatory glutaminergic function at lower doses
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Describe features of dependence and withdrawal (3)
Body compensation - up regulates NMDA receptors increase glutamate function. Chronic, high alcohol intake - GABA and glutamine dysregulation. Alcohol suddenly withdrawn - CNS hyperactivity (seizures)
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How can abstinence be achieved?
Psychological treatments, pharmacological treatments, combination. Agents - acamprosate, disulfiram, naltrexone
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Describe features of acamprosate (1)
Derivative of Taurine which is thought to stimulate GABA-ergic neurotransmission and antagonise effects of excitatory amino-acid neurotransmission. 666 mg TDS with food, with counselling for 1 year. Varied absorption, not metabolised by liver
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Describe features of acamprosate (2)
Excreted via kidney. Crosses BBB. No sedative effect, minimal abuse potential, generally well tolerated
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Describe features of disulfiram (1)
Irreversibly inhibits acetaldehyde dehydrogenase therefore leading to increased levels of acetylaldehyde. Initially 800mg OD, then reduce by 200mg/day to maintenance 100-200mg OD
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Describe features of disulfiram (2)
Duration of treatment varied, need regular review. S/E - nausea, flushing, sweating, headache, thirst, palpitations, hypotension, dyspnoea. Reaction can least 30 mins to several hours. Liver metabolised and renally excreted
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Describe features of disulfiram (3)
Drug interactions - phenytoin (hepatotoxicity), effect may last up to 14 days post discontinuation
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Describe features of naltrexone (1)
Opiate antagonist. Endogenous opioid system may modulate intake of alcohol. Alter opioid receptor activity, decrease alcohol craving and consumption of alcohol. 50 mg OD. IM preparation also available. Liver metabolised and renally cleared
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Describe features of naltrexone (2)
Large adverse effect profile including hepatotoxicity
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What are the key points about treating liver disease? (1)
Patient may present at any stage (need to understand degree of underlying dysfunction). Abstinence is key (psychological, pharmacological methods). Appropriate use of BDZs in management of withdrawal
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What are the key points about treating liver disease? (2)
For AAH - prednisolone used in severe cases but stopped after 7 days if no fall in bilirubin. Management geared with managing complications
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Card 2

Front

What are the causes of liver disease? (2)

Back

NAFLD, drugs and toxins, cancer, biliary tract disorders, infections, other

Card 3

Front

Alcohol is a factor in which medical conditions?

Back

Preview of the front of card 3

Card 4

Front

What are the government recommendations regarding alcohol intake for men and women?

Back

Preview of the front of card 4

Card 5

Front

Give examples of effects of alcohol on the body (1)

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