SA Acute Liver Disease Flashcards
What are some examples of toxic/drug induced causes of acute liver disease (acute hepatitis) in dogs?
- Examples include:
- phenobarbitone
- carprofen (esp. Labrador retrievers)
- potentiated sulphonamides
- environmental toxins e.g. mushrooms
What are some examples of infectious causes of acute liver disease (acute hepatitis) in dogs?
- Examples include:
- Leptospira
- CAV-1. neoneatal canine herpes virus
- bacteria from the GIT i.e. ascending infection via the bile duct – access point possibility. May never locate the bacteria!
How can the clinical signs severity vary with acute liver disease?
Can be low-grade disease: may be mild or non-existent, may miss them and they may come and go – often don’t need treatment, the liver just deals with it
Signs may be due to the underlying cause and/or other body systems involved
As disease progresses or becomes more severe –> more classic signs develop
Clinical signs are often variable and non specific
What are some NON SPECIFIC signs of acute liver disease?
- anorexia
- vomiting/haematemesis
- diarrhoea/melaena
- PU/PD
- jaundice
- dehydration
- fever
- cranial abdominal pain – may mimic pancreatitis, may have all of these things with pancreatitis or acute liver disease
What are some other clinical signs we can see with acute liver disease?
- hepatic encephalopathy
- depression
- seziures
- coma
- Hepatomegaly
- If large and painful, may think more of acute liver diseasae
- evidence of coagulopathy
- petechial haemorrhages
- GI bleeding
- ascites and portal hypertension
- more likely in chronic disease, but sometimes if you have acute, significant swelling of hepatocytes, then it might be that this might be enough to cause portal hypertension
- can occur due to hepatocyte swelling
What are some markers of hepatocellular damage?
ALT, AST increased first
What are some markers of cholestasis?
ALP, GGT increased later
What are some markers of liver function?
- bilirubin – sometimes delayed
- bile acids
- variable and depend on cholestasis
- only useful when bilirubin is normal or only very mildly elevated
- ammonia increased - ammonia is not an easy test to run –needs careful and rapid processing which means it is rarely useful in practice.
- +/- hypoglycaemia
- +/- coagulopathy
How should you manage acute liver disease?
(long one, soz)
- Supportive- very important!
- intravenous fluid support
- avoid lactated ringers solution/Hartmanns
- liver cannot metabolise lactate as the buffer, might be a situation where normal saline might be a better fluid to give than haartmans
- monitor serum potassium and supplement in iv fluids as necessary
- monitor blood glucose regularly and supplement if necessary
- Treat the cause if known, for example:
- antibiotics for leptospirosis
- stop hepatotoxic drugs
- N-acetylcysteine for paracetamol toxicity
- Treat hepatic encephalopathy
- Manage coagulopathy as necessary
- fresh frozen plasma
- Vitamin K therapy might help
- Treat any gastrointestinal ulceration
- GI bleeding can be aggravated by coagulopathy
- Control vomiting
- maropitant: use with caution due to hepatic metabolism – use this if we think acute or live failure case
- consider CRI metoclopramide?
- Diet:
- short period of starvation while any vomiting is controlled
- do not starve for > 24-48 hours – if much beyond this, might need to think about enteral nutrition in these cases
- Anti-emetics
- palatable low fat high quality diet
- do not restrict protein as this may inhibit hepatocyte regeneration – need to keep liver well fed, needs high quality protein
- Other symptomatic and supportive therapy:
- e.g. ursodeoxycholic acid, anti-oxidants
- Antibiotics: broad spectrum agents safe for use in liver disease include:
- ampicillin, amoxicillin, metronidazole (at ¯ dose) and fluoroquinolones.
- use iv in the acute stages
When supporting the acute liver disease patient with fluids, which fluids should you use and which should you avoid and why?
avoid lactated ringers solution/Hartmanns
liver cannot metabolise lactate as the buffer, might be a situation where normal saline might be a better fluid to give than haartmans
What can you give to manage coagulopathy as necesary with acute liver disease?
- Manage coagulopathy as necessary
- fresh frozen plasma
- Vitamin K therapy might help
How can you control vomiting with acute liver disease?
- maropitant: use with caution due to hepatic metabolism – use this if we think acute or live failure case
- consider CRI metoclopramide?
How can you use diet to manage acute liver disease?
- short period of starvation while any vomiting is controlled
- do not starve for > 24-48 hours – if much beyond this, might need to think about enteral nutrition in these cases
- Anti-emetics
- palatable low fat high quality diet
- do not restrict protein as this may inhibit hepatocyte regeneration – need to keep liver well fed, needs high quality protein
Why should you not restrict protein when managing acute liver disease?
do not restrict protein as this may inhibit hepatocyte regeneration – need to keep liver well fed, needs high quality protein
Which antibiotics should you use for the management of acute liver disease?
- Antibiotics: broad spectrum agents safe for use in liver disease include:
- ampicillin, amoxicillin, metronidazole (at ¯ dose) and fluoroquinolones.
- use iv in the acute stages
What is the prognosis for acute liver disease?
- Difficult to predict because varies with extent of damage
- Full recovery is possible but can progress to chronic disease (hepatitis, fibrosis and cirrhosis)
- Severe cases can require a high level of intensive care
- refer to a specialist centre if possible
- Can take a waxing and waning course despite treatment
What are some negative prognostic indicators with regards to the prognosis of acute liver disease?
Negative prognostic indicators include presence of :
- ascites and splenomegaly
- suggests portal hypertension has developed
- can still be reversible in acute disease
How does fibrosis develop with regards to acute liver disease?
What are some examples of canine infectious liver diseases?
- Canine infectious liver disease
- Leptospirosis
- Canine adenovirus 1
- (Canine herpesvirus)
- ((Canine acidophil cell hepatitis))
What is the causal organism of Leptospirosis?
- Causal organism: Leptospirosis interrogans (sensu lato)
- Leptospira spp are motile spirochaetes
- Several serovars can cause clinical signs in dogs
- L. icterohaemorrhagiae (rat host) à liver
- L. canicola (dog host but almost eradicated) à kidney
- L. grippotyphosa (rodent host)
- Others e.g. L. bratislava. L.pomona
How can animals get Leptospirosis?
What is the incubation period?
- Passed in urine –> mixture of direct/indirect transmission
- Organisms penetrate mucosal surfaces and can be absorbed here also
- Incubation period is usually ~ 4–12 days
•
•Clinical disease usually affects liver and kidneys
Where does the clinical disease of Leptospirosis usually affect?
Clinical disease usually affects liver and kidneys
What organ systems do we need to consider with regards to leptospirosis?
•Renal involvement is most common à AKI due to
- swollen tubular epithelial cells
- tubular necrosis
- mixed inflammatory reaction may be seen
•Liver is a target organ
- can be the only site affected – if kidney parameters are normal does not mean the dog doesn’t have lepto. If you have the 2 together – lepto can be very likely
- liver involved in approx. 10-20% dogs with AKI
- gross appearance: swollen and friable
- icterus is common
- microscopic findings may include:
- hepatocytic necrosis,
- nonsuppurative hepatitis
- intrahepatic bile stasis
With leptospirosis, you get acute kidney injury - why?
- swollen tubular epithelial cells
- tubular necrosis
- mixed inflammatory reaction may be seen
Liver is a target organ for Leptospirosis.
What damage does it do and what do we see?
- can be the only site affected – if kidney parameters are normal does not mean the dog doesn’t have lepto. If you have the 2 together – lepto can be very likely
- liver involved in approx. 10-20% dogs with AKI
- gross appearance: swollen and friable
- icterus is common
- microscopic findings may include:
- hepatocytic necrosis,
- nonsuppurative hepatitis
- intrahepatic bile stasis
What are the clinical signs of Leptospirosis?
- Vary with dose, serovar and level of immunity
- Peracute leptospiraemia
- pyrexia, pain, shock, death
- Acute disease
- pyrexia, anorexia, dehydration, PD, V+
- Petechiae and ecchymoses (due to vascultitis +/- ¯ platelets)
- Jaundice (common)
- Oliguric acute renal failure –> anuric renal failure (important to monitor urine output)
- Arthralgia and myalgia
- Dyspnoea- consider “atypical disease” –> pulmonary involvement à LPHS
If you get disease progression with Leptospirosis - what happens in the body?
Disease progression:
- SIRS and MODS –> fatal
- Chronic renal or hepatic failure
What do you see on haematology and biochemistry with Leptospirosis?
- Clinical presentation: any dog that presents with acute liver or renal disease, especially if unvaccinated
- Haematology (cell counts and smear):
- mild to moderate neutrophilia
- thrombocytopaenia (20% cases)
- Biochemistry
- azotaemia
- hyperkalaemia
- elevated liver enzymes
- elevated bilirubin (20% cases)
- Urinalysis: consistent with AKI (30% cases)
- active urine sediment
- Coagulation times normal unless progress to DIC
Definitive diagnosis of Leptospirosis can be very challenging.
What do you see with PCR and antibody titres?
- PCR of organism from urine and blood
- samples collected before antibiotic most helpful
- Antibody titres (MAT)
- if high in unvaccinated dogs could be diagnostic
- need a rising titre in vaccinated dogs
- most convincing is with rising titre (4 fold increase in 2-4 weeks)
- low in chronic disease therefore not helpful for carrier state
- false negative (low) results if antibiotics have been given
What are some things you need to do with the management of leptospirosis?
- Supportive treatment is important: symptomatic patients are often critical care cases
- Supportive
- IVFT – saline, dextrose saline – saline may be better than haartmans
- Manage AKI if necessary:
- to maintain urine output
- furosemide/mannitol/glucose
- to manage electrolyte disorders (esp. hyperkalaemia)
- Control vomiting
- CRI metoclopramide?
- ondansetron?
- low dose maropitant?
- Provide nutrition
- Liver support drugs
- especially SAMe and vitamin E
- other antioxidants
How can you manage AKI with regards to management of Leptospirosis?
Manage AKI if necessary:
- to maintain urine output
- furosemide/mannitol/glucose
- to manage electrolyte disorders (esp. hyperkalaemia)
What is the specific treatment to kill leptospires?
Which drugs are recommended?
Early antibiotic treatment is strongly reccomended
- Penicillin G, ampicillin or ampxycillin for 2 weeks
- kill circulating organisms very effectively
- does not remove the carrier state
- Doxycycline for 2 weeks
- elimination of carrier state
- start with a penicillin
- may cause vomiting and not always tolerated in acute cases – so tend to reserve doxycycline for during recovery phase
Why do you reserve doxycycline for the recovery phase of Leptospirosis?
What shoudl you start with instead?
- start with a penicillin
- may cause vomiting and not always tolerated in acute cases – so tend to reserve doxycycline for during recovery phase
What is the prevention of Leptospirosis with regards to vaccination?
- Inactivated organisms
- Serovars historically have been Icterohaemorrhagica and Canicola
- Newer vaccines now include Australis and Grippotyphosa (ie 4 serovars)
- Duration of immunity variable in different animals
- probably does need annual vaccination unlike other vaccines
- Serology to assess vaccination efficacy?
- correlation between antibody levels and protection is poor
What is the prevention of Leptospirosis with regards to lifestyle?
- reduce access to potential sources of exposure
- avoid drinking from or wading/swimming in fresh or stagnant water sources and marshland
- control rodent sources
- avoid hunting or access to wildlife
What is arrowed here with regards to canine adenovirus 1?
- Tropism for vascular endothelium and hepatocytes
- inclusions in hepatocytes are pathognomonic
What is the prevalence of Canine adenovirus 1?
What is the transmission?
Where does it have tropism for?
- Very low prevalence due to efficacy of vaccine
- usually seen in unvaccinated dogs
- Natural exposure suspected
- non-vaccinated dogs often carry neutralising antibodies
- Transmission: faeco-oral route
- Tropism for vascular endothelium and hepatocytes
- inclusions in hepatocytes are pathognomonic
What are the clinical signs of Canine Adenovirus 1?
(Peracute and Acute)
- Peracute disease
- non-specific rapidly fatal condition without obvious clinical signs
- Acute disease
- clinical signs (5-7 days) associated with hepatic necrosis and diffuse endothelial damage:
- vomiting, diarrhoea, abdominal pain
- jaundice
- petechial or ecchymotic hemorrhages
- DIC may occur due to
- failure of hepatic processing of clotting factors
- endothelial damage
- CNS signs due to HE or encephalitis
What are the ocular clinical signs of Canine Adenovirus 1?
- Ocular signs
- corneal oedema –> blue eye due to
- immune complex deposition – eye and kidney are very susceptible to deposition
- corneal endothelial damage
- anterior uveitis
What is the diagnosis of Canine Adenovirus 1?
- Clinical presentation: any young unvaccinated dog with acute hepatitis
- DD: include leptospirosis, (parvovirus, distemper)
- Haematology (cell count and blood smear)
- leucopenia – early stages neutropenia and lymphopenia
- leucocytosis – recovery stages
- Biochemistry: as expected for acute hepatitis
- ALT, AST> GGT, ALP
- bilirubin
- Prolonged coagulation times +/-DIC
- Confirmation/definitive diagnosis:
- serology (unvaccinated dog)
- PCR (sometimes)
Histologically, what is the main damage to hepatocytes with regards to Canine Adenovirus 1?
Histologically, 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 Canine Adenovirus 1?
Treatment
- Supportive as for any severe acute hepatitis
- We have no specific antiviral drugs that would help
- Outcome depends on
- severity
- development of widespread complications such as DIC
What can septicaemia and endotoxaemia cause?
What can they progress to?
- Both are recognised causes of acute liver disease
- Severity of systemic consequences are usually related to the primary condition
- Cytokines from systemic inflammation/sepsis lead to functional hepatic impairment
- Various changes histologically – non-specific
- Clin path – elevated bilirubin and liver enzymes
- Can progress to SIRS and MODS – liver has blood supply from blood and from normal arterial circulation, therefore double whammy potential of having infectious organisms delivered
- Liver involvement in septicaemic patient – might well be this is the sort of situation that is happeneing
What is hepatic encephalopathy?
HE is a neuro-physiologic disorder of the central nervous system (CNS)
What is the main aim of therapy for the treatment of hepatic encephalopathy?
- Main aim of therapy:
- to decrease formation of gut derived encephalotoxins
- ie decrease ammonia
- Want to minimise toxins, ammonia main one, but there are others.
What is the management of acute hepatic encephalopathy?
- Identify, remove and treat precipitating causes:
- gastrointestinal bleeding
- constipation
- metabolic alkalosis
- Hypokalaemia – complicated! Will precipitate and aggravate hepatic encephalopathy
- azotaemia
- inflammatory disease
- IVFT
- crystalloids (avoid lactated ringers (Hartman’s solution))
- Glucose
- monitor and supplement as needed
- Diet:
- feed a high quality diet little and often ASAP
- protein/calorie malnutrition will increase NH3 formation by catabolism of body protein
- 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 bacteremias
- Gastroprotectants if evidence of gastrointestinal bleeding
What is the dietary management of chronic hepatic encephalopathy?
Dietary management:
- key to the successful management of HE
- feed normal to slightly amounts of protein
- protein source should be high-quality and highly-digestible
- feed small amounts of food several times per day
- We used to think protein restriction was important- no evidence to support this and most dogs with PSS or liver disease might need normal to increased protein.
What is the medical therapy with lactulose for the management of chronic hepatic encephalopathy?
Medical therapy: lactulose
- is a disaccharide which passes into the colon to be degraded by bacteria into SCFAs
- this acidifies the colonic environment trapping NH3 as ammonium ions (NH4+)
- SCFAs (short chain fatty acids) are a preferred energy source for colonic bacteria, causing them to incorporate more ammonia into their own bacterial proteins
- promotes osmotic diarrhoea
- decreased time over which colonic contents are acted on by intestinal bacteria
What is the medical therapy with antibiotics for the management of chronic hepatic encephalopathy?
Medical therapy: antibiotics
- if diet alone, or diet + lactulose, are not effective
- use drugs that are effective against anaerobic organisms:
- metronidazole 7.5mg/kg PO q12h
- amoxicillin 10mg/kg PO q8-12h
