Smallies 6 - Liver Flashcards
What is seen on haematology and biochemistry with lymphocytic cholangitis?
Haematology - mild anaemia +/- leymphpenia and increased neutrophils
Variably increased ALT and ALP
Increased GGT, bilirubin and globulins
What is seen on haematology and biochemistry with hepatic lipidosis?
Haematology - mild/moderate anaemia, heinz bodies
Increased ALT, GGT and bilirubin
Significantly increased ALP
Decreased albumin and potassium
What is seen on ultrasound with neutrophilic cholangitis in cats?
Thickened gallbladder wall? Bile duct distended? Bile sludging Patchy echogenicity \+/- Choleliths? Acoustic shadowing
What is seen on ultrasound with lymphocytic cholangitis in cats?
Hepatomegaly common Heterogeneous appearance Irregular margins Ascites quite common \+/- mesenteric lymphadenopathy
What is seen on ultrasounds with hepatic lipidosis in cats?
Hyperechoic appearance – due to fat
What should be checked before performing a liver biopsy?
Always check coagulation times before a liver biopsy
o Prothrombin time (PT) – same as OSPT
o Activated partial thromboplastin time (APTT)
Why is trucut liver biopsy usually avoided?
Friable tissue – especially with hepatic lipidosis
Only get a very small sample – may not be diagnostic
Other tissue samples often needed (pancreas, intestine, LN)
What tests are used to make a diagnosis of acute neutrophilic cholangitis? And what are significant findings?
Cytology and culture of bile should be definitive - ultrasound guided aspirates may be easier than biopsy
Liver biopsy
- Might be non-specific mild changes
- Hallmark feature – Neutrophilic infiltrate starting within the bile duct lumen and/or epithelium
- Periportal necrosis is common
What tests are used to make a diagnosis of chronic lymphocytic cholangitis? And what are significant findings?
Cytology and culture not consistent with infection (bile and liver) – may help rule out
Liver biopsy - hallmark feature is the lymphocytic infiltrate in portal areas and biliary duct proliferation
What is the main differential of chronic lymphocytic cholangitis in cats?
Lymphoma
What tests are used to make a diagnosis of hepatic lipidosis? And what are significant findings?
Cytology only as cats often too sick to cope with a GA
- Ultrasound guided aspirate safer than biopsy - poor anaesthetic risk so just use sedation
- Evidence of severe lipid accumulation in hepatocytes but don’t confuse with mild secondary lipidosis
Describe treatment for neutrophilic cholangitis in cats
Appropriate antibiotic for a 4-6 week course
o Amoxicillin is a good 1st choice or if no diagnostics
Ursodeoxychilic acid
o Choleretic effects and anti-inflammatory/immune-modulating properties
o Displaces hydrophobic bile acids
Anti-oxidants
o Supportive care if sick (can be septic/SIRS/MODS)
o IVFT +/- potassium, glucose
Enteral nutrition to avoid hepatic lipidosis as a complication
o “IBD diet” or high protein critical care diet – get GIT to settle down, this may help the liver settle down
o Don’t protein restrict
What is the prognosis for neutrophilic cholangitis?
Prognosis can be excellent, leading to a full recovery
Describe treatment for lymphocytic cholangitis in cats
Corticosteroid (+/- chlorambucil as 2nd agent) at immune suppressive doses
Antibiotic treatment - rule out infection if you can do diagnostics?
Ursodeoxycholic acid
Antioxidants (bile is a potent oxidising toxin in the liver) e.g. sAMe or Vitamin E
Enteral nutrition
Supportive care
What is the prognosis for lymphocytic cholangitis?
Waxing and waning disease continues but rarely fatal (cats don’t progress disease with fibrosis the way dogs do)
Describe the treatment for hepatic lipidosis
Enteral feeding ASAP - continue for 4-6 weeks
Anti-emetics (in the acute stage) +/- prokinetics
o Maropitant, metoclopramide
o Ranitidine
IVFT - monitor potassium and glucose
Antioxidants
Vitamin K if any evidence of coagulopathy
Treat the underlying cause/concurrent disease
What is the prognosis for hepatic lipidosis in cats?
Can be good but some cats are very poorly
What can hepatopathy be secondary to in cats?
Hyperthyroidism Diabetes Mellitus Toxic GI disease Pancreatitis Lymphoma
Give examples of hepatic neoplasia in cats
Liver parenchyma - hepatocellular carcinoma
Bile duct - biliary duct adenoma
Why is hepatic neoplasia a common secondary hepatopathy?
Common site for metastases due to excellent blood and lymphatic supply
Name a common systemic neoplasia in cats
Lymphoma
What is a differential for hepatic neoplasia in cats?
Chronic pancreatitis
What is the treatment for hepatic neoplasia in cats?
Surgery unless lymphoma
Are portosystemic shunts congenital or acquired?
Congenital
What are clinical signs of portosystemic shunts?
Subtle, wax and wane Small – “runty-shunty” Seizures – intermittent, complete/partial Dull/manic hehaviour Ptyalism Poor anaesthesia recovery – may detect if the cat is slow to wake up from anaesthesia PU/PD Copper-coloured iris
What should you consider if a young cat is slow to wake up from anaesthesia?
Portosystemic shunt
Normally fine but need a lot of post-op care
Consider running pre and post prandial bile acids at this stage
How is a portosystemic shunt diagnosed?
History and physical exam
Blood results
o High bile acids – pre and post bile acids are best
o Microcytic anaemia – occasionally seen, may also be seen in dogs with a PSS
o (High ammonia)
Ultrasound may demonstrate shunt
Portal-venography (most often extrahepatic)
What is medical management for portosystemic shunts in cats?
Used to advise restrict protein but don’t anymore - add cottage cheese, eggs and rice
Antibiotics e.g. metronidazole, neomycin
Lactulose
What is surgical management for portosystemic shunts in cats?
Stabilise medically first
Beware of the post-operative period - challenging sometimes
- May have seizures, this adversely affects prognosis
Treatment of choice
What are causes of acute liver disease (acute hepatitis) in dogs?
Toxic/drug-induced – major cause but often difficult to find the definitive cause
o Phenobarbitone
o Carprofen (especially Labrador retrievers) and all NSAIDs – idiosyncratic toxicity
o Potentiated sulphonamides
o Environmental toxins e.g. mushrooms
Infectious
o Leptospira
o CAV-1, neonatal canine herpes virus
o Bacteria from the GIT – ascending infection via the bile duct or shed through hepatic portal vein
Sepsis and endotoxaemia
List non-specific clinical signs of acute hepatitis in dogs
Anorexia Vomiting/haematemesis Diarrhoea/melaena PU/PD Jaundice Dehydration Fever Cranial abdominal pain Hepatic encephalopathy – depression, seizures, coma Hepatomegaly Evidence of coagulopathy – petechial haemorrhages, GI bleeding (find via rectal exam) Ascites and portal hypertension
What are markers of hepatocellular damage in dogs?
ALT, AST increase first
What are markers of cholestasis in dogs?
ALP, GGT increase later
What are markers of liver function in dogs?
Bilirubin – sometimes delayed increase
Bile acids – variable and depend on cholestasis. Only useful when bilirubin is normal or only very mildly elevated
Ammonia increased +/- hypoglycaemia (glucogenesis pathways are compromised) +/- coagulopathy
What IVFT should be used in supportive management of acute liver disease in dogs?
Avoid lactated ringers solution/Hartmanns as the liver cannot metabolise lactate as the buffer
Normal saline best in this case but any fluid is better than none
What specific treatment should be given to treat leptospirosis?
IV Antibiotics e.g. doxycycline for 2 weeks
What specific treatment should be given to treat paracetamol toxicity?
N-acetylcysteine
What diet management can be implemented with acute liver disease in dogs?
Short period of starvation while any vomiting is controlled - do not starve for >24-48 hours
Palatable low fat high quality diet
Do not restrict protein as this may inhibit hepatocyte regeneration
Consider use of naso-gastric tube
What broad spectrum antibiotics are safe for use in liver disease?
Ampicillin, amoxicillin, metronidazole (at decreased dose) and fluoroquinolones
What is the prognosis for acute liver disease in dogs?
Difficult to predict because varies with extent of damage
Full recovery is possible but can progress to chronic disease (hepatitis, fibrosis and cirrhosis)
Negative prognostic indicators include presence of
o Ascites and splenomegaly - suggests portal hypertension has developed but can still be reversible in acute disease
o Significant GI bleeding on top of ascites – spiralling out of control, seriously consider euthanasia at this point
Some cases will die despite therapy
Describe the development of fibrosis
Acute injury -> repeated injury -> early fibrosis
- Repeated injury leading to nodular regeneration and fibrosis
- No further injury leads to regeneration of normal lobules
What is the causal agent of Leptospirosis?
Leptospirosis interrogans
Which serovars of Leptospirosis cause clinical signs in dogs?
L. icterohaemorrhagiae (rat host) -> liver
L. canicola (dog host but almost eradicated) -> kidney
L. grippotyphosa (rodent host)
Others e.g. L. bratislava. L.pomona
What organ systems do we need to consider in a Leptospirosis case?
Renal involvment is most common
Liver is the target organ
Why can AKI develop with Leptospirosis?
Swollen tubular epithelial cells
Tubular necrosis
Mixed inflammatory reaction may be seen
What is the gross appearance of the liver with Leptospirosis?
Swollen and friable
Microscopic findings may include hepatocytic necrosis, non-suppurative hepatitis, intrahepatic bile stasis
List clinical signs of peracute Leptospirosis
Pyrexia
Pain
Shock
Death
List clinical signs of acute Leptospirosis
Pyrexia Anorexia Dehydration PD Vomiting
What are haematology findings with Leptospirosis?
Mild to moderate neutrophilia
Thrombocytopaenia (20% cases)
What are biochemistry findings with Leptospirosis?
Azotaemia
Hyperkalaemia
Elevated liver enzymes
Elevated bilirubin (20% cases)
What are urinalysis findings with Leptospirosis?
Consistent with AKI
Active urine sediment e.g. any casts in the urine
What is needed for the suggestive diagnosis of Leptospirosis?
Clinical presentation
Haematology
Biochemistry
Urinalysis
What is needed for the definitive diagnosis of Leptospirosis?
Very challenging
o PCR of organism from urine and blood – send away for external analysis
o Antibody titres (Microscopic Agglutination Test - MAT). But sending a follow up sample in 4 weeks will be too late – treat on the presumption that he has lepto. If high in unvaccinated dogs could be diagnostic but need a rising titre in vaccinated dogs.
o Dark field microscopy – difficult and low sensitivity and specificity,
o Culture of leptospirosis is almost impossible
o Post mortem: Fluorescent in situ hybridisation (FISH) identification of leptospires in tissue samples
What is the supportive treatment for Leptospirosis?
IVFT – saline, dextrose saline Manage AKI if necessary Control vomiting Provide nutrition Liver support drugs - Especially SAMe and vitamin E
How can Leptospirosis be prevented?
Vaccination
Reduce access to potential sources of exposure e.g. open water (especially stagnant) and rats
How is canine adenovirus 1 (CA-1) transmitted?
Faeco-oral route
What is the causative virus of CA-1?
Family: Adenoviridae
Genus: Mastadenovirus
What are clinical signs of peracute CA-1?
Non-specific rapidly fatal condition without obvious clinical signs
What are clinical signs of acute CA-1?
Clinical signs (5-7 days) associated with hepatic necrosis and diffuse endothelial damage:
Vomiting, diarrhoea, abdominal pain
Jaundice
Petechial or ecchymotic haemorrhages
DIC may occur due to failure of hepatic processing of clotting factors or endothelial damage
CNS signs due to HE or encephalitis
What ocular signs can be associated with CA-1?
Corneal oedema -> blue eye due to immune complex deposition or corneal endothelial damage
Anterior uveitis
What is included in the diagnosis of CA-1?
Clinical presentation Haematology Biochemistry Prolonged coagulation Confirmation by serology (unvaccianted dog) or PCR
What are differentials for CA-1?
Leptospirosis
Parvovirus
Distemper
What is seen on haematology with CA-1?
Leucopenia – early stages neutropenia and lymphopenia
Leucocytosis – recovery stages
What is seen on biochemistry with CA-1?
As expected for acute hepatits
Increased ALT, AST > GGT, ALP
Increased bilirubin
What is seen on histology of the liver with CA-1?
The main damage is to hepatocytes and endothelium (blood vessels – hence the haemorrhaging)
The liver contains areas of necrosis and adenoviral inclusion bodies are seen in Kupffer cells and parenchymal cells
What is the treatment for CA-1?
Supportive as for any severe acute hepatitis, we have no specific antiviral drugs that would help
What is the prognosis of CA-1?
Outcome depends on severity and development of widespread complications such as DIC
What is seen on the clinical pathology with sepsis and endotoxaemia?
Elevated bilirubin and liver enzymes
What is hepatic encephalopathy?
Neuro-physiologic disorder of the central nervous system that occurs in patients with advanced, acute (sudden) or chronic (long-term) liver disease
What is the main aim of therapy with hepatic encephalopathy?
To decrease formation of gut derived encephalotoxins i.e. decrease ammonia
What is needed in the management of acute hepatic encephalopathy?
Identify, remove and treat precipitating causes e.g. gastrointestinal bleeding, constipation, metabolic alkalosis, hypokalaemia, azotaemia, inflammatory disease
IVFT e.g. crystalloids (avoid lactated ringers (Hartman’s solution))
Glucose - monitor and supplement as needed to prevent hypoglycaemia
Diet - feed a high-quality diet little and often asap
Warm water/lactulose enemas to remove any source of ammonia from the faeces, can be followed by a neomycin retention enema
Ampicillin IV to protect against bacteraemias
Gastroprotectants if evidence of gastrointestinal bleeding
What is needed in the management of chronic hepatic encephalopathy?
Dietary management is key to the successful management of HE. Feed normal to slightly increased amounts of protein
Lactulose orally (chronic) or enema (acute)
Antibiotics if diet alone, or diet plus lactulose, are not effective. Use drugs that are effective against anaerobic organisms e.g. Metronidazole or Amoxicillin
What are causes of chronic liver disease?
Idiopathic chronic hepatitis Copper-associated liver disease True copper storage disease Congenital vascular disease Neoplasia Biliary tract disease
What is the most common liver disease in dogs?
Idiopathic chronic hepatitis
What breeds is copper-associated liver disease associated with?
Labrador retriever, Dalmatian, Sky terrier, Doberman pinscher
WHWT: some (but not all) have copper accumulation
What breed of dog has true copper storage disease?
Bedlington terriers
Give examples of primary neoplasia causing chronic liver disease in dogs
Hepatocellular carcinoma
Lymphoma
Give examples of biliary tract disease that cause chronic liver disease in dogs?
Biliary mucoceles
Neutrophilic cholangitis
Extrahepatic bile duct obstruction
Bile duct rupture
What is are typical histological findings with canine chronic hepatitis?
A variable mononuclear or mixed inflammatory infiltrate
See lymphocytes and plasmocytes rather than neutrophils – chronic
Hepatocellular apoptosis or necrosis
Regeneration and fibrosis
Which breeds have an increased prevalence of canine chronic hepatitis?
Cairn terrier, Dalmatian, Doberman Pinscher, English Cocker Spaniel, English Springer spaniel and Labrador Retriever
What is the typical clinical history of chronic hepatitis in dogs?
Waxing and waning non-specific clinical signs including
o Inappetence
o Weight loss
o Vomiting +/- haematemesis if GI ulceration
o Diarrhoea +/- melena
o PU/PD
o Lethargy, depression true neuro signs/HE?
Early signs can be missed or misdiagnosed as self-limiting GI disease - dogs present in an “acute” crisis but could be “acute on chronic” disease
What are important clinical findings in a dog with chronic hepatitis?
Poor body condition, jaundice and ascites
What is seen on biochemistry in a dog with chronic hepatitis?
Liver enzymes
o Variable increase in ALT and ALP
Markers of liver function
o Decreased albumin and urea
o Increased bilirubin, bile acids (fasting and post prandial) and NH3 (
o Prolonged coagulation times
What is seen on ultrasonography in a dog with chronic hepatitis?
Might get the impression the liver is small
Irregular liver margination
Variable echogenicity: often patchy hyper- and hypoechogenicity
Ascites
Acquired PS shunts (typically seen caudal to left kidney – may see a bunch of blood vessels)
You won’t necessarily see all of these. If the liver looks normal but everything else suggests chronic hepatitis it’s still likely
List drugs commonly used in the treatment of chronic hepatitis in dogs
- Destolit (ursodeoxycholic acid)
- Antioxidants: SAMe, Silybin, vitamin E
- Corticosteroids
- Antibiotics
- Diuretics – sometimes the ascites will remain and the dog will just get dehydrated
What is the justification for ursodeoxycholic acid as part of the treatment for chronic hepatitis in dogs?
UDA is a hydrophilic bile acid which displaces hydrophobic (toxic to liver cells) bile acids
Draws water into biliary system i.e. it has choleretic effects
Is potentially immune-modulating – might help to dampen down some inflammatory pathways
Prevents cells entering the apoptosis pathway
Increased production of glutathione
What is the justification for antioxidants as part of the treatment for chronic hepatitis in dogs?
Oxidative damage from reactive oxygen species (ROS) is common in many hepatopathies including chronic hepatitis
What is the main antioxidant used to protect the liver against oxidative damage?
Glutathione (GSH)
What other antioxidants do we use in liver disease?
S adenosyl methionine (SAMe) Silybin (milk thistle) Vitamin E Commercial products available and licensed for use: o Denamarin (Protexin) o Zentonil Advance (Vetoquinol)
What is the justification for corticosteroids in the treatment for chronic hepatitis in dogs?
- Anti-inflammatory
- Immune-modulating
- Anti-fibrotic
When should we avoid corticosteroids in the treatment for canine chronic hepatitis?
- End-stage/cirrhosis/bridging fibrosis – will cause more harm than good with steroids at this point
- Ascites/GI ulceration (=portal hypertension)
What are the potential adverse effects of corticosteroids if used in a dog with chronic hepatitis?
Increased protein catabolism can cause or worse hepatic encephalopathy
Fluid retention can cause (or worsen) ascites
Ulcerogenic effects leading to GI ulceration
o Dexamethasone is more ulcerogenic than prednisolone
Increased risk of infection or exacerbates existing infections
What is the justification for antibiotics in the treatment of canine chronic hepatitis?
Management of hepatic encephalopathy – decreases NH3 formation
If histopathology from biopsy changes suggests
o Ascending cholangitis – suggesting the disease is ascending from the gut
o Significant neutrophilic component to any inflammation
There is often very little justification for giving antibiotics in chronic liver disease i.e. very different to acute liver disease (e.g. leptospirosis)
Histopathological changes might indicate antibiotics could be used
What is the pathophysiology of ascites secondary to canine chronic hepatitis?
1) Pooling of blood in the splanchnic circulation
2) Decreased arterial blood pressure
3) Activation of RAAS
4) Fluid retention and ascites
How do we manage ascites?
Spironolactone – aldosterone antagonist. Have a 2-3 day delay before effect
Furosemide (can dehydrate patient rather than help) – with spironolactone if poor response
Peritoneal drainage if life threatening?
o Releases pressure which will give the patient some relief
o Reforms rapidly, causes dehydration (fluid taken form vasculature) and aggravates decrease in albumin
What is the role of dietary management of canine chronic hepatitis? And discuss components of the diet
Protein - high quality, highly digestible protein sources ideal e.g. chicken, soya, dairy (especially cottage cheese)
o Do not restrict protein intake excessively unless signs of HE
Carbohydrates - use a highly digestible source e.g. rice, pasta, potato, intestinal type diet
Fat - Only restrict fat if steatorrhoea develops
Fibre - Soluble and insoluble fibre are good
Liver support diets are also restricted in copper – helps avoid situations where Cu storage compromises the liver any further
Why should white fish not be used as a protein source for a dog with chronic hepatitis?
It is high in purines which can lead to development of hepatic encephalopathy
What is the typical presentation of True Copper Storage Disease?
Bedlington Terriers Young dogs: acute hepatic necrosis and haemolysis (rare) Older dogs (4 yrs +): chronic hepatitis cirrhosis
What is True Copper Storage Disease?
Specific defect in biliary Cu excretion due to autosomal recessive conditoin
Similar to the situation with copper toxicosis in sheep - the liver stores Cu and in association with stress can suddenly release liver leading to a haemolytic crisis and/or hepatic necrosis
What is needed to diagnose True Copper Storage Disease?
Liver biopsy from 12 mths of age for a Cu assay
Genetic test
