Hepatic disease Flashcards
What can cause acute liver injury/ failure?
Prolonged ischaemia Drugs Toxins Neoplasia Metabolic disorders Infectious disease (e.g. Lepto) Immune-mediated disease
What toxins can cause acute liver injury/ failure?
Aflatoxins Amanita mushrooms Blue-green algae Cycad palms Xylitol
What drugs can cause acute liver injury/ failure?
Phenobarb Paracetemol Oral benzodiazepines (cats) Carprofen Lomustine Mititane Sulphonamides Zonisamide Itra/kenoconzaole Glipizide Methimazole/ carbimazole Rifampicin Tetracycline
Which infections can cause acute liver injury/ failure?
FIP Lepto Infectious Canine Hepatitis Salmonellosis Toxoplasmosis Platynosum fastosum
How can acute liver injury cause hepatic encephalopathy?
Combination of hyperamonaemia, excitatory neurotoxicity, oxidative stress, altered permeability of the blood-brain barrier, inflammation, neurosteroid-induced GABA receptor modulation within the CNS
What can precipitate hepatic encephalopathy?
Hypokalaemia (increases renal tubule ammoniogenesis)
Hyponatraemia (risk factor for cerebral oedema)
Metabolic acidosis (facilitates ammonia diffusion into the CNS)
Can you have normal ammonia levels and hepatic encephalopathy?
Yes
How can you manage seizures caused by hepatic encephalopathy?
Leviteracetam ideally, can also do propofol
There is some evidence that diazepam may play a role in the pathogenesis of HE so avoid if possible
What other treatment should be given for hepatic encephalopathy apart from controlling seizures?
Emergency - warm water cleansing enema (10mL/kg) to reduce the number of ureae-producing bacteria in the colon
Follow with a lactulose retention enema, then oral
Metronidazole (lowered dose of 7.5mg/kg) or ampicillin
Manitol if intracranial pressure is suspected due to cerebral oedema
Avoid excessive protein restriction as this may increase ammonia in the blood due to endogenous protein catabolism (monitor protein levels by measuring albumin). Ideal is a heptaic diet with cottage cheese added
Why/ when give antimicrobial prophylaxis in acute liver injury/ failure?
Secondary infection is a major cause of death
Only give when there is a vasopressor non responsive hypotension, progression or HE, positive culture of infection
Give a broad spec AB
Why give antacids with liver injury/ failure?
High risk of gastro-duodenal ulceration Omeprazole H2 agonist Also sucralfate Evidence that gastric pH is elevated with liver disease, so the effects of an H2 agonist are unclear
Why make vitamin K be low with acute liver injury/ failure? (empiric therapy recommended)
Poor oral intake
intra or extra hepatic cholestasis
AB use may affect the microbiome and reduce vit K2 producing bacteria
What is the prognosis for acute liver injury/ failure?
Low, one study said 14%
Why do animals with liver disease get ascites?
Normally due to portal hypertension
Only sometimes is it hypoalbuminaemia
How do you treat ascites in liver disease?
If low protein - high quality protein, e.g. soya or cottage cheese
Portal hypertension - (tx underlying thing also!) Spironolactone over frusemide, K+ sparing. Can take 2-3 days for effect. Only use frusemide to speed things up.
Do not drain unless it is life threatening (rare)
Why is GI ulceration common with liver disease
Portal hypertension leads to gut wall oedema, leads to ulceration
When should you not use metoclopramide with liver disease
When there is HE
When should maropitant be avoided with liver disease?
Significant liver dysfunction (metabolised by the liver)
What is the antacid of choice for liver disease?
Ranitidine
Which antacid is indicated for paracetemol toxicity?
Cimetidine - involved with P450
What is the antidote for paracetemol toxicity?
N-acetylcysteine - a glutathione precursor.
It binds the toxic metabolite and increases glucoronidaton.
SAM-e also useful to replenish glutathione, which inactivates the toxic metabolite
How do you treat potentiated sulphonamide toxicity?
N-acetylcysteine also useful, treat the signs.
How do you treat phenobarb toxicity?
Some dogs develop hepatocutaneous syndrome on long term therapy
Ideally withdraw and replace with a drug not metabolised by the liver (e.g. KBr)
SAM-e v useful as it is a precursor for antioxidant and detoxifying systems of the liver
What is the typical appearance of hepatocutaneous syndrome on ultrasound
Liver has a swiss cheese appearance
What bacteria are associated with hepatitis?
E.coli Enterococcus Klebsiella Clostridium Faecal Strep Corynebacterium
What should be included in the treatment for suppurative cholangitis?
Manage clinical signs
Antibiotics (penicillins/ cephalosporins/ fluoroquinolones)
Destolit to encourage bile flow
High quality protein diet - normally a critical care diet it best
What causes copper storage disease in bedlington terriers?
Defect in the transport of copper from hepatic lysosomes
How should you treat copper associated hepatitis?
Low copper diet (only prevents further build up)
Anti-oxidants e.g. SAM-e and Vit E
Destolit
Chellation with penicillamine or 2,2,2-tetramine if hepatic copper levels are high or rising
How should you treat chroinc hepatitis?
Palatable high quality protein diet supplemented with zinc, B vitamins, antioxidants. Do not restrict protein unless there are signs of HE
Antibiotics if there is a significant neutrophilic component or ascending infection
Treat ascites as needed
Steroids id there is significant inflammation without fibrosis
Colchicine if there is significant fibrosis
What are the likely US appearances of the following diseases? Hepatitis Nodular hyperplasia Vacuolar hepatopathy Fibrosis Hepatocellular carcinoma Lymphoma Metastasis Necrosis Lipidosis Haemangiosarcoma Steroid hepatopathy Degeneration
Hepatitis - Multifocal, hypoechoic OR Diffuse, heteroechoic
Nodular hyperplasia - Multifocal, hypoechoic
Vacuolar hepatopathy - Diffuse, hyperechoic
Fibrosis - Diffuse, hyperechoic
Hepatocellular carcinoma - Multifocal, heteroechoic
Lymphoma - Multifocal, hypoechoic
Metastasis - Multifocal, hyperechoic
Necrosis - Diffuse, hyperechoic
Lipidosis - Diffuse, hyperechoic
Haemangiosarcoma - Multifocal, heteroechoic
Steroid hepatopathy - Diffuse, hyperechoic
Degeneration - Diffuse, hyperechoic
Outline the use of steroids in liver disease
Used for their immune-modulating/ anti inflammatory or anti fibrotic actions
Very rarely indicated for use in acute liver disease as they are contra-indicated for use when there is portal hypertension
n.b. immune mediated liver disease in dogs has not been convincingly proven yet
When SHOULD steroids be used for liver disease?
There is biopsy evidence of inflammation
There is no fibrosis, or only very mild fibrosis associated with inflammatory infiltrate
Infectious causes have been ruled out as much as possible
When should steroids NOT be used in liver disease?
Known or suspected infectious disease
Advanced, bridging fibrosis or non-inflammatory fibrosis (high risk of serious adverse effects due to the associated portal hypertension)
Ascites - This is normally caused by portal hypertension
Hepatic encephalopathy - steroids lead to protein catabolism and the production of amonia/ other encephalopathic compounds
Acute hepatatis - Animals with acute hepatitis tend to have an infectious or toxic origin and are high risk for ulceration. Only give when there is a specific indication
Why are steroids bad with portal hypertension?
use of steroids precipitates gastrointestinal ulceration
This then precipitates hepatic encephalopathy as a result of bleeding into the intestinal lumen
Steroids also increase water retention
Always avoid dexamethasone as it has high ulcerogenic capacity
What other liver drugs may have anti-inflammatory effects besides steroids?
SAM-e
Destolit
colchicine
Zinv
When are antibiotics used for liver disease?
Tx of HE
When there is infection (bacterial cholangitis is rare)
If there is a suspicion of cholangitis, definitely try to culture as there is a high risk of bacterial resistance in these patients
Outline the use of colchicine
Anti fibrotic
For cases of marked to moderate fibrosis confirmed on biopsy
Monitor animals for bone marrow suppression
Can cause anorexia and d+ than necessitates ceasing of treatment
Unclear how effective it is in dogs - good in people
Would require repeat biopsy to assess response
alkaloid that binds tubulin and has the potential to reverse fibrosis
When is metronidazole useful
Very effective agains anaerobes
Often used in combination with ampicillin/ amox
Reduce the dose to 7.5mg/kg as it is metabolised by the liver
Also for HE
When are fluoroquinolones useful?
For bacterial cholangitis or when gram negatives are suspected
Poor agains anaerobes or strep
Good penetration in liver and bile
Do not use in growing dogs
Never use enrofloxacin in cats due to retinal damage
Which antibiotics that rely on hepatic clearance or are hepatotoxic should be avoided?
Tetracyclines
Sulphonamides
Chloramphenicol
Erythromycin
What antioxidants are there?
Vitamin E Silymarin SAM-e Zinc Logical to use but no clear evidence that they improve the quality of life of the animal/ survival
Outline the use of SAM-e
Increases hepatic and RBC glutathione levels
Especially good for toxic hepatopathies (e.g. phenobarb), may also be good for steroid hepatopathis
Indicated for all types of liver disease, esp also for biliary stasis
Outline the use of vitamin E
Effective anti-oxidant
Use in cases of copper storage disease as levels of vitamin E are reduced in hepatocytes
What is Ursodeoxycholic acid?
Bile acid modifyer
Hydrophilic bile acid that displaces toxic hydrophobic bile acids and stimulates bile flow (ie, it is a choleretic).
This reduces cell damage and oxidative stress resulting from the retention of bile acids in the liver
Also an immune-modulator
Also shows antioxidant activity with a synergistic action with SAM-e and vitamin E
Indicated in all forms of liver disease, although contra-indicated in complete bile duct obstruction
What copper chelators are there (for copper storage disease)
Penicillamine is the most commonly used, however can take weeks to months for an effect
Zinc can be used as a prophylactic
Also 2,2,2-tetramine tetrahydrochloride (2,2,2-T) - not available in the UK
All have side effects, use with caution
Outline palatability/ times requirements for feeding a liver patient
Feed a palatable diet little and often (four to six times a day) as many animals with liver disease may be
anorexic.
Feeding little and often minimises hepatic work and signs of encephalopathy
Outline the protein requirements for a liver patient
Most dogs with liver disease have increased protein requirements.
Highly digestible, high-quality protein should be fed in normal amounts
Consider supplementation with cottage
cheese, chicken or soya when using a commercial
reduced-protein hepatic diet.
White fish should be avoided as it is high in purines. Protein should only be restricted when there is HE Serum albumin concentrations should be monitored to allow adjustment of dietary protein levels
Outline the carb requirements of a liver diet
Dogs with liver disease have impaired carbohydrate metabolism.
Highly digestible complex carbohydrates
should be fed (eg, rice, potato or pasta)
Outline the fat requirements of a hepatic patient
Normal levels unless steatorrhoea develops
Outline the fibre requirements of a hepatic patient
Fermentable fibre is helpful in animals with hepatic encephalopathy as it acidifies the colon and so
traps ammonia.
It also increases nitrogen incorporation into bacteria and reduces bacterial ammonia production.
Non-fermentable fibre helpful in preventing constipation, a predisposing factor for
hepatic encephalopathy.
Lactulose is a synthetic disaccharide that acts as a soluble fibre
