Hepatobiliary disease Flashcards
What gene is associated with copper storage disease and in which breed?
COMMD1
Bedlington Terrier
Which breeds are predisposed to hepatic amyloidosis?
Abyssinian, Oriental, Siamese, Chinese Shar-Pei
What is the median age of presentation of animals with multiple acquired PSS?
3y
What breed is predisposed to progressive vacuolar hepatopathy? What other condition is it associated with?
Scottish Terriers
Hepatocellular carcinoma
What are the presenting signs of hepatocutaneous syndrome in dogs and cats?
Dogs - hyperkeratosis footpads, erythema/ulcerations of perioral, perianal, perivulval, preputial skin
Cats - ulceration/crusting of mucocutaneous junction, pinnae, periocular, interdigital areas, central abdomen (NOT FOOTPADS)
How is portal hypertension classified - give examples
Pre-hepatic - extra hepatic portal vein (atresia, fibrosis, thrombosis, neoplasia), arteriovenous fistulas
Intra-hepatic - pre sinusoidal, sinusoidal, post sinusoidal (chronic hepatitis with fibrosis)
Post-hepatic - post hepatic CVC/RA - R-CHF, pulmonary hypertension, Budd Chiari
How does peritoneal fluid differ between conditions causing ascites through PH?
Pre-hepatic/pre sinusoidal/sinusoidal - low protein content (<2.5g/dL)
Post hepatic, post sinusoidal, sinusoidal - high protein content (>2.5g/dL)
What is the mechanism of HE in cats with hepatic lipidosis?
Cat’s can’t synthesis arginine - depleted with fasting
Arginine necessary for completion of urea cycle
Which liver enzymes are leakage or inducible?
Leakage - ALT/AST
Inducible - ALP/GGT
What % of hepatic neoplasia have normal liver enzymes?
50%
What is the T1/2 of ALT in dogs/cats?
D - 48-60h
C - 6h
What is the T1/2 of AST in dogs/cats?
D - 22h
C - 77mins
Where is AST found?
Liver, muscle, RBCs
Where is ALT found?
Liver»_space;> muscle
What can cause AST > ALT
Muscle/RBC origin
Where in the cell are ALT/AST found?
ALT - cytosol
AST - 80% cytosol, 20% mitochondria
Where is ALP found (list in descending order)
Intestinal mucosa, renal cortex, placenta, liver, bone
What is the T1/2 of ALP in dogs and cats?
D - 70h
C - 6h
What is the sensitivity/specificity for of ALKP for liver disease in dogs/cats
D - 81/50%
C - 50/93%
What is the mechanism of ALKP elevation in hyperthyroid cats?
Bone isoenzyme
Where is GGT found (list in descending order)
Kidney, pancreas, liver, gallbladder, intestine, spleen, lungs, erythrocytes
In cats how to ALKP and GGT compare with a) hepatic lipidosis, b) necroinflammatory liver disease?
a) ALP > GGT
b) GGT > ALP
How much hepatic function must be lost for hypoglycaemia to occur?
75%
How much hepatic function must be lost for hypoalbuminaemia to occur?
70%
What liver condition has been associated with hyperalbuminaemia?
Hepatocellular carcinoma
What condition other than about it disease or anaemia is associated with jaundice?
Sepsis
Cytokines inhibit the expression of hepatocyte transporters necessary for bilirubin transport
What is the mechanism for a patient remaining jaundiced after the resolution of bile duct obstruction?
Conjugated bilirubin binds irreversibly with albumin forming delta-bilirubin. T1/2 2 weeks
Which hormone stimulates gallbladder contraction?
Cholecystokinin, secreted from the duodenal mucosa in response to fat or protein
Where are bile acids absorbed?
Ileum
What is the reported sensitivity and specificity of bile acid stimulation for diagnosis of a PSS?
99%/95-100%
What is the reported sensitivity and specificity of fasted ammonia for diagnosis of a PSS?
98/89%
How does the liver affect haemostasis?
1 - produces all clotting factors except VW-subtype of FVIII
2 - cholestasis causes malabsorption of vit K
3 - AT III, protein C and S synthesised in liver
4 - PH => splanchnic pooling and increased capturing of platelets
5 - fibrinogen - acute phase proteins produced in excess = increased fibrinogen consumption
How can PSS and PVH be differentiated?
Reduced protein C activity in PSS but not PVH
Which breeds are predisposed to the formation of ammonium urate crystals without hepatic insufficiently?
Dalmatian, English bulldog, Siamese cats
What are the mechanisms for polyuria in patients with hepatic disease?
Loss of renal medullary hypertonicity, impaired hormone metabolism and psychogenic polydipsia
Which radiographic view has the best correlation with liver weight in dogs?
Right lateral
What is the reported agreement of cytologic and histologic diagnosis in the liver sampling?
30-60%
What percentage of patients with a histopathological diagnosis of hepatic neoplasia had neoplastic cells detected on cytology?
50%
What is the reporter discordance between tru-cut and wedge liver biopsy?
50%
What is the mechanism of SAMe?
Central role in synthesis of glutathione - essential antioxidant
May have anti-inflammatory, anti-carcinogenic and apoptosis modulating effects
What is the mechanism of N acetylcysteine?
Replenishes intracellular cysteine and glutathione concentrations
What is a concern about the long-term use of N acetylcysteine?
May lead to impairment of ammonia metabolism by the urea cycle
What is the mechanism of sillymarin?
Free radical effects, anti-inflammatory effects, may inhibit hepatic fibrosis, may act as choleretic
What medication has proven effective for Amanita mushroom toxicity?
Silymarin (IV)
What is the mechanism of UDCA?
Hydrophilic bile acid, displaces harmful hydrophobic bile acids, choleretic, cytoprotective, immunomodulatory.
What is the mechanism of D-penicillamine?
Chelaitng agent, combines with copper allowing mobilisation from the liver and excretion in the urine. May have antifibrotic effect.
What are the short and long term side effects of D-penicillamine.
GI
Copper deficiency - microcytic hypo chromic anaemia, anorexia. vomiting, weight loss
What is an alternative medication that can be used in dogs who do not tolerate D-penicillamine?
Trientine
How does trientine differ from penicillamine. When might it be a good first option?
Removes more copper from circulating pool and less from tissue pool
Cu-related haemolysis
How does zinc reduce copper?
Induces metallothionein by enterocytes - bind Cu, prevents absorption
What non-hepatic clinical signs are associated with CAV-1 infection?
Bronchopneumonia, conjunctivitis, anterior uveitis and corneal oedema
What infectious agents have been associated with acute hepatitis in dogs?
CAV-1, lepto, clostridium, E. canis
In which zones of the liver does copper accumulate in a) copper storage disease and b) secondary copper accumulation?
a) Zone 3 (centrilobular)
b) Zone 1 (periportal)
According to WSAVA classification, what are the 4 types of cholangitis?
Neutrophilic, lymphocytic, destructive, chronic associated with liver fluke
Which liver enzyme is most consistently elevated in feline cholangitis?
AST
How often is bile culture in cats positive? What are the common isolates?
36%
E.Coli + anaerobes
What is the most common biochemical abnormality in cats with lymphocytic cholangitis?
Hypergammaglobulinaemia
Which parasite is associated with infectious chronic cholangitis in cats?
Where is it seen geographically?
What are its hosts?
How is it treated?
Platynosomum
North, South, Central America, Caribbean, parts of Africa and Asia
Lizards, snails, isopods
Praziquantel
What viral diseases are associated with liver disease in cats?
FeLV, FCV, FIP, FIV
Which fungal diseases are associated with liver disease in cats?
Histoplasma, Coccidioidomycosis, Blastomyces, Aspergillosis, Cryptococcus, Sprothrix
How much blood is supplied to the liver by the portal vein and hepatic artery respectively?
80/20%
Are IH or EH PSS associated with more severe clinical signs?
IH
Which breeds are predisposed to EHPSS?
D - YT, Havanese, Maltese, Dandie Diamont, Pug, Miniature Schnauzer
C - DSH, Persian, Siamese, Himalayan, Burmese
What type of PSS is most commonly seen in cats?
EHPSS
Which breeds are predisposed to IHPSS and what type do they get?
Left divisional - Irish Wolfhound
Right divisional - Australian Cattle Dog
Retrievers and Australian Shepherds - either
What aspects of shunt morphology are associated with the degree of clinical signs observed?
High
Portocaval, insertion caudal to liver, splenocaval (CNS), right gastric (urinary)
What haematological changes are reported in dogs/cats with PSS?
Microcytic normochromic anaemia
D - Target cells
C - Poikilocytes
How to coagulation abnormalities differ in dogs with acute and chronic liver failure?
Chronic - PT elevation only
Acute - PT/aPTT
What testing should be done in an animal with HE and hyperammonemia without evidence of a PSS?
Urine metabolic screen
For urea cycle abnormalities (ornithine carbamylase deficiency, methymalanic acidemia)
What are positive prognostic indicators for dogs with PSS managed medically?
Older age and higher urea level
What is the prognosis for medical management of PSS?
> 50% PTS within 10 months
~33% can survive long term
What proportion of dogs with EH / IH PSS tolerate complete occlusion?
EH - 32-52%
IH - <15%
What are the potential manifestations of acute/chronic portal hypertension following PSS ligation?
Acute - ascites, intestinal congestion, diarrhoea, hypoxaemia, bowel death
Chronic - MAPSS
What proportion of dogs are reported to redevelop clinical signs following shunt attenuation?
40-50%
Following temporary shunt occlusion what portal pressures are associated with increased postoperative complications?
> 9-10cm water above resting
17-24cm water absolute
What gradual occlusion devices for PSS are available?
Ameroid constrictors
Cellophane bands
With ameroid constrictor placement what is the;
a - complication rate
b - mortality rate
c - rate of good to excellent outcomes
a - 7-20%
b - 0-17%
c - 94%
With cellophane band placement what is the;
a - complication rate
b - mortality rate
c - rate of good to excellent outcomes
a - 10-13%
b - 3-9%
c - 84%
What is the reported surgical complication rate with IHPSS?
29-77%
What is the reported incidence of post ligation seizures unrelated to HE following PSS attenuation?
12%
What clinical signs post PSS attenuation indicate worrisome portal hypertension?
Vomiting, ascites, abdominal pain, hypotension
What is a specific complication seen following attenuation of IHPSS? How can the risk be reduced?
GI bleeding
Lifelong gastric acid suppression
How does the prognosis of PSS in cats and dogs differ?
Cats have higher post operative complication rates and worse long term outcomes (particularly due to neurological sequelae)
What is the pathophysiology of HAVM?
Increased portal pressure due to high pressure arterial blood shunting into PV => multiple acquired shunts
What factors are associated with poor long term outcome in dogs with EHPSS?
Hypoalbuminaemia, leukocytosis, post-op seizures, persistent shunting at 6-10 weeks
What factors are associated with good short term outcome in dogs with IHPSS?
Higher bodyweight, TP, albumin, BUN
What are the treatment options for HAVM and the prognosis?
Surgery along - 75-91% survival
Glue embolisation - 100%
What is the complication rate in PSS attenuation in cats?
Complications in 75%
0-23% mortality rate
On histopathology how can hepatic glycogen and fat accumulation be differentiated?
PAS - glycogen
Oil red O - fat
What are the possible causes of vacuolar hepatopathy in dogs and cats?
Steroid (endogenous/exogenous)
Vacuolar hepatopathy of Scottish Terriers
Cobalamin deficiency (dogs)
Secondary (CHF, neoplasia, hepatobilliary disease, GI, renal, infectious)
Where are changes seen in different stages of steroid hepatopathy?
Starts in centrilobular region (one 3)
Becomes generalised when chronic
What biochemical changes are seen with steroid hepatopathy in dogs?
ALKP elevation - poss due to reduced clearance of intestinal isoenzyme
Which breed is associated with glycogen-like vacuolar hepatopathy? What other disease is associated with it?
Scottish Terriers
HCC
50% have clinical signs of HAC - poss related to precursor form
What conditions are associated with hepatic steatosis?
Hepatic lipidosis (C)
Vit A toxicosis (C)
Aflatoxicosis (D)
Secondary to hyperlipidaemia
Endocrine disease (hypothyroidism, DM, hyperthyroidism)
PSS
What types of steatosis are described histopathologically? Which types are typically seen with DM and HL?
Microvesicular - vacuoles smaller than cell nucleus
Macrovesicular - larger vacuoles, often displacing nucleus
DM - micro
HL - micro + macro
What types of FHL are recognised?
Primary - overweight cats after prolonged fasting
Secondary - associated with other disease
What are the common clinical examination findings in FHL?
Hepatomegaly and jaundice
What are the typical biochemical findings in FHL?
Elevated ALT, ALKP, bilirubin
GGT often normal if primary
What is the diagnostic test of choice for FHL? What is the limitation of other options
Histopath
Cytology can give false +ve
What are the mortality rates of FHL with and without assisted feeding?
Without - 90%
With - 40%
What food is most appropriate to feed cats with HL?
High protein - shown to reduce hepatic lipid effectively in experimentally induced FHL
What is the pathogenesis of the skin lesions in SND?
Amino acid deficiency
What % of cases of SND have signs of DM?
25-40%
What is the classical histological findings of SND?
Parakeratotic hyperkeratosis with inter and intracellular oedemas
Red, white and blue on H + E
What is the cause of hemochromatosis?
Iron overload of the liver
Only secondary reported in dogs - normally associated with Cu
What are the 2 forms of amyloid?
Normal - soluble
Abnormal - auto-aggregating fibrillar form of beta-pleated sheets
Which breeds of cats are associated with amyloidosis and how do they present?
Abyssinian - renal (+/- hepatic involvement)
Siamese - often hepatic
How do cats with hepatic amyloidosis present?
Acute abdominal bleed secondary to liver fracture
Jaundice, hepatomegaly
Which lysosomal storage disease with predominantly hepatic signs is reported? Which breed is affected?
Lipid storage disorder, Fox Terriers
What are the two mechanisms of drug induced hepatotoxicosis?
Cytotoxic
Cholestasis
What are R values? How are they calculated and used?
Used in people to differentiate cytotoxic and cholestatic liver injury
R = (ALT/upper limit normal)/(ALKP/upper limit normal)
<2 cholestatic, 2-5 mixed, >5 hepatocellular
What is the rationale of treating paracetamol toxicity with NAC?
Reactive metabolite; NAPQI detoxified by conjugation with glutathione. NAC = glutathione precursor
What has been suggested as a treatment for methaemoglobinaemia secondary to paracetamol toxicity?
Ascorbate
What has been reported as an effective treatment for blue-green algae toxicosis?
Cholestyramine
What has been reported as an effective treatment for Amanita toxicosis?
Silybin
Are primary or metastatic liver tumours more common in cats/dogs?
D - metastatic
C - primary
What are the 4 tissue types of liver tumours?
Hepatocellular, bile duct, neuroendocrine, mesenchymal
What is the most common liver tumour in dogs?
Hepatocellular adenoma/carcinoma
What is the most common liver tumour in cats?
Bile duct adenoma
What predilections are reported for canine bile duct tumours?
Breed - Labradors
Sex - Female
What neuroendocrine tumours are reported in dogs and cats, how do they typically behave?
Carcinoids
Biologically aggressive and diffuse
What are the most common primary mesenchymal hepatic tumours in dogs/cats?
D - leiomyosarcoma
C - Haemangiosarcoma
How to biochemical abnormalities differ between primary and metastatic liver tumours?
Primary - more likely to have low protein, low glucose, increased ALKP, less likely to have elevated TBil
What biomarker has been reported to be elevated in HCC and bile duct carcinoma?
Alpha-fetoprotein
What chemotherapy has been described for treatment of nodular/diffuse HCC?
Gemcitabine, mitoxantrone
What are the treatment options for nodular/diffuse bile duct carcinomas?
No effective treatment described
Which breeds are predisposed to cholelithiasis?
Mini Schnauzers and Mini Poodles
What types of choleliths are reported in dogs?
Cholesterol, bilirubin and mixed
What is the significance of biliary sludge in dogs/cats?
Dogs - common incidental finding
Cats - often indicative of cholecystitis
What gallbladder wall thickness accurately predicts gallbladder disease in cats?
> 1.0mm
What rare manifestation of cholecystitis is described? What is it’s aetiology and what treatment should be recommended?
Empysematous cholecystitis
Usually associated with E Coli and Clostridium
Surgery
What risk factors have been associated with GBM?
Dyslipidaemia, gallbladder dysmotility, endocrine disease (HAC), exogenous steroids
What is the link between steroids and GBM formation?
Steroids increase levels of unconjugated bile acids - more hydrophobic => biliary injury => mucin secretion increases
