Hepatic Flashcards
Breed predispositions to PVH without PH
Maltese
Cairn
Yorkies
What type of cPSS is most often seen in cats?
Extra-hepatic
What degrees of hyperbilirubinaemia are expected for:
- Seeing icteric plasma
- Seeing icteric MM
- 8 - 18umol/L
- > 50 - 85umol/L
Which type of portal hypertension is a high protein (rather than low protein) ascitic fluid expected in?
Lower protein is expected in pre-sinusoidal portal hypertension
Which amino acid is of particular importance in the urea cycle and therefore deficiencies of this can result in hepatic encephalopathy?
Arginine - cats with cysteine stones can therefore be hyperammonaemic due to arginie loss through COLA transporters
ALT:
- T 1/2 in the dog
- T 1/2 in the cat
- Alternative source from the liver
Dog: 48 - 60h
Cat: 6h
Muscle is the other main source
AST
- T 1/2 in the dog
- T 1/2 in the cat
- Alternative sources
- Dog: 22h
- Cat: 77 minutes
- Sources: muscle, RBC
ALP
- T 1/2 in the dog
- T 1/2 in the cat
- Alternative sources
Dog 70h
Cat: 6h
Sources: intestinal mucosa, renal cortex, placenta, liver, bone
In dogs can be induced by steroids
GGT
- T 1/2 in the dog
- T 1/2 in the cat
- Alternative sources
T 1/2 is unknown
Sources: Kidney>pancreas>liver>GB>intestine>spleen>heart>lungs>skeletal muscle>RBCs
CK
- T 1/2 and kinetics with muscle injury
Peak concentration occurs within 6 - 12 hours of muscle injury and will decline within 24 - 48 hours.
Degree of reduction in hepatic mass to result in hypoglycaemia
0.75
Degree of loss of liver mass required for hypoalbuminaemia
0.7
Which globulins are produced by the liver?
Alpha and beta globulins, although hypoglobulinaemia is rare in hepatic disease
What are the potential causes for increased pre-prandial rather than post-prandial bile acids?
Inter-digestive gallbladder contraction
Variations in gastric emptying and intestinal transit times
Varied responses to CCK
What is the indication for performing and ammonia tolerance test? how is this test performed?
- 2ml/kg of 5% ammonium hydrochloride administered 10 - 20cm into the rectum via a catheter
- Take basal, 20m and 40m sample
- Normal response is minimal increase in ammonia
Which coagulation factors are not produced by the liver?
vWF and a subtype of factor VIII
What is the indication for measurement of protein C and the clinical cut off of activity?
To help differentiate PSS from PVH. Activity <70% is indicative of PSS
What percentage of dogs with PSS may have ammonium biurate crystals?
0.5
What conditions is a hypoechoic liver parenchyma associated with?
Acute hepatitis
Amyloidosis
Lymphoma
Cholangitis/Cholangiohepatitis
I.e. it is still non-specific
What is a normal CBD diameter in dogs and cats?
3mm dogs and up to 4mm in cats
Where in the abdomen is MAPSS more likely to be identified using AUS, what other findings can suggest MAPSS?
Left dorsal perirenal area
Reduced portal blood flow (<10m/s)
Hepatofugal flow
Enlarged PV and dilated left gonadal vein
What are the three weird and wonderful methods of evaluating for a PSS?
Portal scintigraphy with Tc99m-sulfur-colloid
Pre-rectal portal scintigraphy
Trans-Splenic Portal Scintigraphy
Outline the basis of and interpretation of Tc99m-Sulfur-Colloid scintigraphy
- Small colloidal particles that localise to the reticuloendothelial system
- In normal animals it should mostly be present in the liver
- In PSS a large amount may occur in the lungs
However, this can also occur with other causes of liver insufficiency in dogs and occurs normally in cats.
Outline the basis and interpretatino of pre-rectal portal scintigraphy
- Administration of a radionucleotide into the colon (usually sodium pertechnetate)
- In normal patients it should first be seen in the liver and then in the heart.
- In PSS it will be seen in the heart first. However, with small shunts it could reach both at the same time.
Computer programming can calculate a shunt fraction
What are the disadvantages to this technique?
○ Can have poor uptake from the colon –> non-diagnostic study
○ Poor anatomic detail, so determining the type and anatomy of the shunt can be challenging
○ False negatives if infused too high into the rectum
○ Need for isolation post procedure
Outline the basis of and interpretation of trans-splenic portal scintigraphy
- Ultrasound-guided injection of radiopharmaceutical (sodium pertechnetate) into the splenic parenchyma.
- In the normal animal this should be absorbed into the splenic vein which will then flow into the left gastric vein and then the main portal vein.
- Can miss shunts that enter the portal vein caudal to the splenic vein
Small shunts may be missed as well.
Which liver disease does FNA have the best PPV for?
Hepatocellular carcinoma followed by non-hepatocellular carcinomas and round cell tuours
Which hepatoprotectant has evidence for use in acute amanita phalloides toxicity?
Intravenous silmaryn
In hepatic disease which version of pred (prednisone vs. prednisolone) is more appropriate and why?
Prednisone needs to be converted to prednisolone to the liver so prednisolone is probably a better choice
What are the two chelating agents available for the treatment of copper hepatopathy?
D-penicillamine
Trientine
What is the mechanism by which Zinc reduced hepatic copper accumulation?
It results in ncreased synthesis of metallothionein by enterocytes which binds copper in enterocytes preventing its movement into the circulation and liver.
What are the four WSAVA classifications of cholangitis?
Neutrophilic
Lymphocytic
Destructive
Chronic associate with liver fluke
Infectious causes of acute canine hepatitis
Toxic causes of acute canine hepatitis
Drugs that may result in acute canine hepatitis
What clinical sign of hepatic disease is not expected with acute liver injury?
Ascites
What clinical signs outside of hepatic and general systemic signs may be seen with CAV-1 infections?
- Bronchopneumonia
- Conjunctivitis
- Photophobia
- Corneal opacity from anterior uveitis
Which leptospirosis spp. are zoonotic?
L. interrogans and kircheri
What specific treatment should be given to dogs with blue-green algae toxicity?
Cholestyramine - this blocks re-absorption of bile acids and may therefore prevent microcytins being absorbed. Otherwise the treatment is all supportive.
What does the COMMD1 mutation result in?
Failure of hepatocytes to be able to excrete copper into bile
What is the histologic localisation of copper when primary vs. secondary?
Zone 3 (centrilobular) = primary
Zone 1 (periportal) = secondary
I guess this makes sense as the liver is trying to move it to the bile in primary cases but in secondary cases it can’t move?
What stain is used to evaluate for hepatic copper?
Rubenaeic acid/rhonadine
What is the histopathologic distinction between cholangitis and cholangiohepatitis?
Cholangitis is limited to inflammtory changes within the bile duct luen and between biliary epithelial cells. It inflammation extends beyong the limiting plate (layer of hepatocytes that border the portal tract)
What percentage of cats with neutrophilic cholangitis are icteric vs. hyperbilirubinaemic?
34% icteric, 66% hyperbilirubinaemic
What percentage of bile and liver samples will culture positive in cases of neutrophilic cholangitis?
36% bile samples and 14% liver samples
How long should antibiotics for hepatic abcesses be given for?
Minimum of 6 weeks and should consider surgical or percutaneous drainage
Where in the united states might Platynosomum (Liver Fluke) be expected?
Platynosomum fastosum is a liver fluke of cats in Florida, other areas of the southeastern United States, and Hawaii.
What are the paratenic hosts of platysonomum?
Lizards, land snails and isopods (crustaceans e.g. woodlice)
Platynosomum egg and adult images
What do these images depict?
Platynosomum egg and adult images
Which feline viral diseases have been implicated in inflammatory liver diseae and which are potentially primary pathogens?
FeLV - primary hepatic degeneration and fatty liver
FIP - pyogranulomatous inflammation
FIV - secondary disease
FCV - mutated form can cause disseminated disease
What is the mechanism by which acetaminophen causes toxicity?
Acetaminophen is converted to NAPQ1 which is a reactive metabolite. It is normally conjugated to glutathione to prevent toxicity.
Which speices differnce between cats and others makes them prone to acetaminophen toxicity?
They lack UGT1A6 - this is a glucoronidation enzyme
They may also have reduced ABCG2 transporters which are responsible for the export of acetaminophen
What is the mechanism by which N-acetyl cysteine exerts its effect?
NAC is a glutathione precursor
Which drug could theoretically be used in acetaminophen toxicity, why, why is it not used?
Cimetidine should reduce oxidation of acetaminophen to NAPQ1 but this has not been shown to work in vitro studies
Can phenobarbital cause liver toxicirty?
Yes! This can be indicated by increased ALT>ALT or changes in liver function parameters. If BA increase then the possibility of toxicity should be considered.
Which anti-fungals are of concern for causing hepatotoxicity?
Ketoconazole
Itraconazole
Fluconazole
What is the mechanism by which azoles cause hepatotoxicity?
Metabolites (such as N-deacetyl-ketoconazole) bing to liver proteins and deplete glutathione
Which breed of dog may be at increased risk of azathioprine toxicity?
GSD
What percentage of dogs will experience increased ALT as a result of lomustine? Which breed has increased risk?
30%
Boxers are at increased risk
MoA of TMPS hepatotoxicity
Immune mediated
Which species of fungus produces the hepatotoxin alfatoxin B1
Aspergillus
What is the mechanism of toxicity of aflatoxins?
dose dependent DNA damage and glutathione depletion
What is the toxin produced by amanita species that results in toxicity? What is the mechanism of toxicity?
amatins mostly alpha-amatin hich inhibits RNA polymerase
What are the clinical squalae to amanita toxicity?
Hepatotoxicity
Hypoglycaemia (through direct insulin release, occurs first)
Rental tubular necrosis
Which organisms are responsible for blue-green algae toxicity in freshwater and ocean water?
Actually caused by cyanobacteria
- Microcytisis aurogenosa in freshwater
- Nodularia spumigena in ocean water (can also cause renal toxicity)
What is the mechanism of toxicity of cyanobacteria?
they inhibit hepatic serine/threonint phosphatases which leags to hyperphosphorylation and disruption of cytoskeletal proteins
What is the mechanism of toxicity of cycad palms?
Cycasin is converted to methlazoxmethanaol by gastrointestinal flora which can result in GI, hepatic and neurologic toxicity
Which specific drug has beneficial effect in the managemnet of cycad palm toxicosis?
Activated charcoal
Differences between hepatic tumours in cats and dogs
Dogs - ore likely to have metastatic diseases, primary tend to have hepatocellular origin, more likely malignant.
Cats - more likely to have primary, biliary tumours more often benign
What are the morphologic classifications of hepatocellular carcinoma?
- Massive = single large tumour confined to one lobe
- Nodular - multifocal wiht distinct nodules
- Diffuse = coalescing nodules or diffuse effacement of hepatic parenchyma
What breed of dog is predisposed to hepatocellular carcinoma?
Miniature schnauzers
Which liver lobes are predilection sites for hepatocellular cacinoma?
left lateral, medial and caudate lobes for massive carcinomas
What are the main metastatic sites for hepatocellular carcinoma?
Lymph nodes, peritoneum and lung
What is the metastatic rate of massive vs. nodular/diffuce hepatocellular carcinoma?
Massive up to 37% and other forms more like 93 - 100%
What immunohistochemical marker may be useful in determining linage of hepatocellular tumours?
Keratin 19
>5% positivity may indicate progenitor cells that are more likely to metastasise
What is the name for primary hepatic neuroendocrine tumours?
Hepatic carcinoid
Which chemotherapy agent may be the treatment of choice for dogs with nodular/diffuse hepatocellular carcionma?
Gemcitabine, mitoxantrone may be another choice
What is the anatomic difference between dogs and cats that potentially predisposes cats to triaditis?
In dogs the CBD joins the pancreatic duct at the duodenal papillar, in cats the CBD and pancreatic duct fuse prior to exit at the duodenal papilla
What is the component of bile that cats differ to dogs?
Cats have higher degrees of calcium so probably more likely to develop calcium containing choleliths
Where might choleliths be expected on abdominal radiographs?
Cranioventral abdomen on a lateral radiograph
Right cranial abdomen on a VD radiograph
How long does it take for extra vs. intra-hepatic duct dilation to occur in cases of obstruction?
Extra-hepatic within 24 - 48 hours of complete obstruction
Intra-hepatic within 5 - 7 days of obstruction
What bilirub concentration in abdominal fluid should prompt concern for bile duct rupture?
?2x that of serum
Which antimicrobials are mostl ikely to be effective for treamtent of cholecytitis
Fluroquinolones (e.g. ciprofloxacin) and aminoglycosides
Which bacterial organisms cause an emphysematous colitis?
Gas producing organisms such as E. coli and Clostridium perfringens
What is the life cycle of liver fluke? How does it infect the cat?
Embryonated eggs are ingested by terrestrial snails which is then passed on from the snail to an isopod where cercariae form and lizards then ingest the isopod. Metecercariae develkop in the lizard which is then eaten by the cat. The metececariae migrate through the biliary tree and reside there in the cat. Cats pass embryonated eggs in faeces.
What are the sequalea to liver flukosis?
Inflammatory changes as expected but cholangiocarcinomas can also develop with chronic infection
How are liver flukes diagnosed in faeces?
Need sedimentation techniques
Review metabolites involved in the pathogenesis of HE
See piece of paper
Vascular anomalies and genetic basis (if known) in the following breeds:
- Yorkshite terrier
- Maltese
- Irish wolfhound
- Australian cattle dog
- Cairn terrier
-
- YRK: OR 35.9 for PSS
- Maltese - autosomal recessive predisposition to PVH and macroscopic shunts
- Irish Wolfhound: left divisional
- Australian cattle dog: right divisiona
- Cairn: hereditary PVH
Which breed of dog seems to be overrepresented in cases of PVH with portal hypertension
Dobermans
What are the mechanisms of action of lactulose in hepatic encephalopathy?
- Acidification of colonic contents leads to ammonia trapping
- Decreases numbers of bacteria
- Increases GI transit time which clears bacteria and ammonia
How should the management of a PSS attenuation patient be tapered?
Medical management continued for approximatley 1 month after surgery and then tapered gradually based on clinical signs. Bile acids are likely to remain elevated post-operatively but there is no impact on survival.
What are the main causes of the following vacuolar hepatic changes:
- Glycogen/water type
- Fat type
What stains can be used to differentiate between water/glycogen and fat accumulation in hepatocytes?
PAS for glycogen
Oil red O for fat
What percentage of hepatocytes need to be affected to diagnose fulminant hepatic lipidosis?
> 50%
What diseases has superficial necrolytic dermatitis been associated with in dogs?
Glucagonaoma, insulinoma and phenopbarbital toxicity
What does this picture indicate? What disease process should you be concerend about?
Swiss cheese appearance of liver, this should prompt concern for superficial necrolytic dermatitis which may be secondary to a glucagonoma
What is the pathophysiology of hepatic lipidosis?
- Increased peripheral lipolysis results in increased triglyceride accumulation in the liver.
- Reduced ability for the liver to oxidise fats leads to further accumulation
- Protein deficiency, particulary amino acids taurine and cartinine deficiency impair apoprotein production preventing transport of fats outside of the liver
Which liver enzyme should not be increased in primary hepatic lipidosis?
GGT - aslthough can be increased with underlying causes
What percentage of hepatocytes need to be affected by fat accumulation on FNA of the liver to raise concern for HL?
> 80%
Treatment for hepatic lipidosis
- Fluids
- Electrolyte supplementation: potassium, phosphate, magnesium)
- Feeding
- Vitamin K
- B-vitamin supplementation
- Vitamin E
- L-carnitine supplementation
Which infectious aitiologies have strong and poor evidence for cause of chronic hepatitis
Leptospirosis and leishmania have the best evidence
E. canis, Babesia and anaplasma have weak evidence
Which 5 toxins are possible causes of chronic hepatitis?
Phenobarbital
Phenytoin
Primidone
Lomustine
Which canine breeds are predisposed to copper associated chronic hepatitis
Bedlington
Dalmatian
Labrador
Dobermans
WHWT
What is the genetic mutation responsible for copper hepatopathy in bedlington terriers (dont use COMMD1)
ATP7B - autsomal recessive deletion of exon 2
What are the diagnostic criteria for copper hepatopathy as outlined in the consensus statement?
- Histopathologic evidence of chronic hepatitis along with centrilobular (zone 3) copper accumulation
- Quantitative copper >1000ug/g d/w liver
Note that > 600 ug/g is the grey zone
What other clinical syndromes can result from copper hepatopathy?
Haemolytic anaemia (due to copper release)
Fanconi-like syndrome
Which miRNA is specifically discussed in the chronic hepatopathy consensus statement?
miR 122
What is the key biochemical screening test/criteria for suspicion of CH in dogs?
Increased ALT that persists for > 2 months
What is the reccomended method of obtaining and number of biopsy specimens when performing liver biopsy
Minimum of 5 biopsies from 2 lobes
3x for histopath
1x for culture
1x for copper
What amount of copper in a liver biopsy specimen should be considered an indication for a copper restricted diet?
> 600ug/g dry weight
Four mechanisms of action of D-penicillaine
Binds hepatic copper
Increases hepatic metallothionein which detoxifies copper
Increases enterocyte metallothionein which allows faecal excretion
Has weak anti-fibrotic and anti-inflammatory effects
How can D-pen therapy be monitored and tapered?
ALT, treat for 1m beyond resolution of ALT
What rare side effects of D-pen are there?
Proteinuria
Skin eruptions
Induction of ALP
