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Ettinger Notes > Hepatobiliary > Flashcards

Hepatobiliary Flashcards

1
Q

Liver toxins: environment

A

cycad palms
amanita mushroom
aflatoxin
blue-green algae

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2
Q

Liver toxin: food

A

xylitol

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3
Q

Liver toxin: chemicals

A

heavy metal

arsenic

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4
Q

Liver toxins: drugs

A

acetaminophen, amiodarone, azathioprine, carprofen, corticosteroids, diazepam (cat, oral), diethylcarbamazine-oxibendazole, doxycycline, griseofulvin (cat), halothane, ketoconazole, lomustine, mebendazole, methimazole (cat), methotrexate, mitotane, nitrofurantoin, phenazopyridine, phenobarbital, stanozolol (cat), sulfonamides, tetracycline, thiacetarsamide, zonisamide

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5
Q

Liver infections: bacterial

A

lepto
mycobacterium tuberculosis
escherichia coli
clostridium perfringens

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6
Q

Liver infections: viral

A

canine adenovirus-1

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7
Q

Liver infections: fungal

A

blastomyces dermatitis
cryptococcus neoformans
histoplasma capsulatum
coccidioides immitis

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8
Q

Liver infections: parasitic

A

platynosomum fastosum
toxoplasmosis
schistosomiasis
migrating larvae

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9
Q

when can you see icterus?

A

serum bilirubin > 3 mg/dL (up to 5)

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10
Q

when can you see icteric plasma?

A

bilirubin > 0.5-1 mg/dL

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11
Q

what is the most common cause of ascites in liver disease?

A

portal hypertension, although decreased vascular oncotic pressure form hypoalbuminemia may play a role

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12
Q

causes of prehepatic portal hypertension?

A

increased resistance in extra hepatic portal vein; associated with mural or intraluminal obstruction (congenital atresia or fibrosis, thrombosis, neoplasia) or extraluminal compression; hepatic AV fistula

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13
Q

typical signalment & presentation of patient with prehepatic portal hypertension?

A

young
ascites
hepatic encephalopathy

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14
Q

causes of intrahepatic portal hypertension?

A

increased resistance in microscopic portal vein tributaries, sinusoids, or small hepatic veins. divided into presinusoidal, sinusoidal, post sinusoidal
ex: chronic hepatitis w/fibrosis or cirrhosis

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15
Q

most common cause of intrahepatic portal hypertension?

A

chronic hepatitis with fibrosis or cirrhosis

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16
Q

causes of post hepatic portal hypertension?

A

obstruction of larger hepatic veins such as post hepatic caudal vena cava or right atrium. ex) right heart failure, pericardial disease, pulmonary hypertension, Budd-Chiari syndrome

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17
Q

what is the protein content in prehepatic portal hypertension

A

low protein (<2.5 g/dL)

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18
Q

what is the protein content in pre-sinusoidal portal hypertension

A

low protein (<2.5 g/dL)

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19
Q

what is the protein content in post-sinusoidal portal hypertension

A

high protein (>2.5 g/dL)

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20
Q

what is the protein content in post-hepatic portal hypertension

A

high protein (>2.5 g/dL)

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21
Q

what is the protein content in sinusoidal intra-hepatic portal hypertension

A

could be high or low, more likely high (>2.5 g/dL)

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22
Q

toxins implicated in hepatic encephalopathy?

A

ammonia, aromatic amino acids, bile acids, endogenous benzodiazepines, gamma aminobutyric acid, glutamine, phenol, SCFA, tryptophan, decreased alpha-ketoglutarate, false neurotransmitters

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23
Q

why might chronic hepatic encephalopathy occur in cats?

A

hepatic lipidosis: cannot synthesize arginine in the liver, and depletion of arginine occurs w/prolonged fasting. arginine is necessary for completion of urea cycle; without it, ammonia detoxification is impaired

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24
Q

ALT half-life

A

dog: 48-60h
cat: 6h

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25
Q

AST half-life

A

dog: 22h
cat: 77 min

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26
Q

where is AST found?

A

liver, muscle, RBC

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27
Q

where is ALT found?

A

liver&raquo_space;> muscle

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28
Q

pattern of CK increase after muscle injury

A

increases quickly, peak levels 6-12 hours post-injury

half-life is short, so decreases w/in 24-48h post injury

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29
Q

how much of AST is in mitochondria?

A

20%

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30
Q

why is AST less sensitive than ALT for detecting hepatic injury?

A

20% is in mitochondria

shorter half-life

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31
Q

why is AST less specific than ALT for detecting hepatic injury?

A

found in blood & muscle as well as liver

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32
Q

which of the following would cause the biggest increase in ALT? hepatic neoplasia, cirrhosis, hepatocellular necrosis & inflammation, biliary tract dz (obstructive), biliary tract dz (nonobstructive)

A

hepatocellular necrosis & inflammation

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33
Q

in acute liver disease, a decrease of XX% or more of ALT over a few days is considered a good prognostic sign

A

50%

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34
Q

what attaches ALP to cell membranes?

A

glucosyl phosphatidylinositol linkages

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35
Q

which liver enzyme has the lowest specificity for hepatobiliary dz?

A

ALP

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36
Q

in dogs, what is the sensitivity and specificity of ALP for hepatobiliary disease?

A

sens: 80%. spec: 51%

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37
Q

where is ALP found in the dog?

A

in descending order of how much: intestinal mucosa, renal cortex, placenta, liver, bone

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38
Q

plasma half life of L-ALP (dog & cat) & C-ALP (dog)

A

dog: L & C: 70 hr
cat: L: 6hr

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39
Q

in the cat, what is the sensitivity and specificity of ALP for hepatobiliary disease?

A

sens: 50%
spec: 93%

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40
Q

in what feline endocrine disease may B-ALP contribute significantly to elevations in ALP?

A

hyperthyroidism

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41
Q

in dogs, what is the sens & spec of GGT for hepatobiliary dz?

A

sens 50%, spec 87%

concurrent incr in ALP increase spec to 94%

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42
Q

in cats, what is the sens & spec of GGT for inflammatory liver dz?

A

sens 86%, spec 67%

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43
Q

how can GGT & ALP help differentiate type of liver dz in a cat?

A

hepatic lipidosis (underlying cause isn’t necroinflammatory): ALP relative to upper limit will be greater than magnitude of incr GGT. necroinflam liver dz: incr in GGT of greater magnitude than incr in ALP

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44
Q

hypoglycemia occurs after what % of liver function is lost?

A

75%

occurs d/t reduction of hepatic glycogen stores, gluconeogenesis, & clearance of insulin

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45
Q

hypoalbuminemia occurs after what % of liver function is lost?

A

70%

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46
Q

hyperalbuminemia has been reported in patients with what disease?

A

hepatocellular carcinoma

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47
Q

which globulins is the liver responsible for making?

A

alpha & beta

gamma-globulins come from B lymphocytes & plasma cells

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48
Q

how does cholesterol help you define type of liver dz?

A

hypo: end-stage liver dz
hyper: cholestatic liver dz

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49
Q

why do you see increase in globulins with PSS or decreased hepatic mass?

A

decreased filtration & clearance of toxins & microbial agents form portal circulation

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50
Q

why is there an increase in bilirubin with sepsis?

A

cytokines inhibit expression of hepatocyte transporters necessary for bilirubin transport
can occur w/o the presence of hepatobiliary dz

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51
Q

you can see hyperbilirubinemia with which artifacts?

A

hemolysis & lipemia

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52
Q

what % of cats with hepatic lipidosis have hyperbilirubinemia?

A

> 95%

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53
Q

how might an EHBDO affect feces?

A

absence of stercobilin = acholic feces

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54
Q

what is delta bilirubin?

A

bile duct obstruction - conjugated bilirubin in plasma binds irreversibly covalently with albumin (delta bilirubin); half-life is 2 weeks = can stay icteric for several weeks despite resolution of bile duct obstruction

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55
Q

patients with a congenital PSS are or are NOT likely to be icteric? why?

A

are NOT: bilirubin is not affected by abnormal liver perfusion.

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56
Q

bile acids are synthesized from what?

A

cholesterol (in the liver)

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57
Q

what hormone is the major stimulus for GB contraction? where does it come from? in response to what?

A

cholecystokinin, from the duodenal mucosa, in response to fat or protein in ingesta

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58
Q

what is the process of enterohepatic circulation?

A

GB contraction -> bile goes from GB to duodenum (to solubilize dietary lipids), then reabsorbed in the ileum & transported back to liver via portal vein, where 95% of bile acids are removed & process starts all over again

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59
Q

pre & post prandial bile acids are what % sens/spec for diagnosis of PSS?

A

99% sens, 95-100% spec

fasting alone: dog - 93% sens, 67% spec; cat - 100% sens, 71% spec

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60
Q

how can lipemia change bile acids?

A

false increase

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61
Q

what clin path abnormality can anorexic cats with liver disease get? why?

A

hyperammonemia: lack of arginine, which is an essential substrate for detoxification of ammonia in the urea cycle

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62
Q

hepatic dysfunction must cause a xx% reduction in urea cycle function in order for hyperammonemia to result

A

70%

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63
Q

sens/spec of elevated fasting ammonia for dx PSS?

A

sens 98%, spec 89%

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64
Q

describe the procedure for an ammonia tolerance test

A

give 2mL/kg of 5% NH4Cl deep into rectum. measure ammonia pre- & 20 & 40min post-administration

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65
Q

liver produces which clotting factors?

A

all except the von willebrand subtype of factor VIII

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66
Q

how does cholestasis affect clotting?

A

causes malabsorption of fat-soluble vitamins (ie vitamin K)

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67
Q

which are the Vet K dependent clotting factors?

A

2 7 9 10 protein C protein S

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68
Q

most common coagulation abrnomality in cats with hepatobiliary dz?

A

increased PT

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69
Q

which clotting inhibitory proteins are produced in the liver?

A

antithrombin III, protein C, protein S

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70
Q

what is hypersplenism? it occurs secondary to what disease?

A

splanchnic pooling of blood can lead to prolonged capturing of platelets at their degradation site in the spleen -> thrombocytopenia
occurs secondary to portal hypertension

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71
Q

coag parameters associated with DIC?

A

low fibrinogen
thrombocytopenia
prolonged PT & aPTT
elevated FDP & D-dimers

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72
Q

what is protein C?

A 
disulfide-linked glycoprotein
molecular weight similar to albumin
synthesized in liver
circulates as plasma zymogen
once activated, binds protein S -> together they exert anticoagulant effects by degrading factors Va &amp; VIIIa
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73
Q

half life of protein C

A

6 hours

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74
Q

protein C less than XX% is common in patients with PSS but rare in MVD

A

70% (seen in 88% of PSS, 5% of MVD patients)

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75
Q

what CBC abnormalities are commonly seen with hepatic disease?

A

microcytosis (associated with impaired iron transport in patients with vascular abnormalities),
target cells,
poikilocytosis,
heinz body formation (cats),
anemia d/t hemorrhage from GI ulceration / coag disorder / anemia of chronic dz,
+/- mild thrombocytopenia

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76
Q

what UA finding in cats is specific for liver disease?

A

bilirubinuria (can also be seen with hemolytic dz)

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77
Q

why can dog urine have bilirubin in it normally?

A

low renal threshold for bilirubin excretion, and kidneys have enzymes needed to produce bilirubin from heme & to conjugate it

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78
Q

what crystals can be found in urine of dogs & cats with PSS? why?

A

ammonium biurate
due to reduced conversion of uric acid to allantoin & of ammonia to urea. ammonia & uric acid aggregate in acidic urine to form crystals

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79
Q

what breeds are associated with developing ammonium biurate crystals w/o hepatobiliary dz?

A

dalmation
english bulldog
possibly siamese cats

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80
Q

what UA finding might a patient with copper storage hepatopathy have?

A

fanconi-like: glycosuria w/normal BG, +/- proteinuria

due to copper accumulation in renal tubules

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81
Q

why do patients with hepatobiliary dz have a low USG?

A

loss of renal medullary hypertonicity d/t low BUN
impaired hormone metabolism: decreasing cortisol metabolism -> Cushing’s-like syndrome
psychogenic polydipsia

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82
Q

measurements from what imaging modality & view has the highest correlation with actual liver weight in dogs?

A

measuring right lateral abdominal radiographs

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83
Q

discuss CT versus AUS for diagnosis of PSS

A

CT-angio: sens 96%, spec 89%

CT-angio is 5.5x more likely to correctly determine presence/absence of cPSS than AUS

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84
Q

discuss technetium for diagnosing PSS

A

Tc-sulfur colloid: colloidal particles that localize in reticuloendothelial system. normal dogs - localize in liver. PSS - localize in lung. not specific for PSS. cats - lung uptake is normal

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85
Q

discuss per-rectal portal scintigraphy

A

normal - pertechnetate goes liver -> heart. PSS: bypass liver; goes to heart first.

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86
Q

trans-splenic portal scintigraphy: describe path of uptake

A

normal: spleen - splenic vein - left gastric vein - main portal vein - liver - hepatic sinusoids - hepatic vein - caudal vena cava - heart
can distinguish between portoazygous & portocaval/splenocaval shunts

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87
Q

what is glutathione?

A

tripeptide synthesized from L-glutamate, L-cysteine, & glycine
essentail antioxidant
stored in hepatocytes

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88
Q

why should care be exercised when giving stored RBC to dogs/cats with acute liver injury

A

ammonia concentrations can increase during storage

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89
Q

why are patients with acute liver injury sometimes vitamin K deficient?

A

cholestasis

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90
Q

where is copper found in primary copper hepatopathy?

A

centrilobular zone of liver

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91
Q

where is copper found in secondary copper hepatopathy? why does it accumulate?

A

periportal zone of liver; secondary to cholestasis

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92
Q

what is the pathophysiology of hepatic fibrosis?

A

chronic hepatic inflammation leads to activation of myofibroblasts including hepatic stellate cells & portal fibroblasts, which cause hepatic fibrosis. oxidative injury can also lead to hepatic stellate cell activation

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93
Q

what are the 4 groups of cholangitis, according to WSAVA?

A

neutrophilic, lymphocytic, destructive, and chronic cholangitis associated with liver fluke infestation

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94
Q

causes of acute canine hepatitis: infectious

A

canine adenovirus-1, leptospirosis, clostridium, canine monocytes ehrlichiosis (E canis)

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95
Q

causes of acute canine hepatitis: toxins

A

mycotoxin, aflatoxicosis, cyanobacteria (microcystin toxicosis - blue green algae), amanita mushrooms, xylitol, manganese overdose (joint supplement), alpha lipoid acid, organic solvents (CCl4)

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96
Q

causes of acute canine hepatitis: drugs

A

carprofen, acetaminophen, TMS, azathioprine, amiodarone, mitotane

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97
Q

symptoms of CAV-1

A

fever, lethargy, anorexia, cranial abdominal pain, melon, vomiting, diarrhea, chem - liver & kidney involvement, bronchopneumonia, conjunctivitis, photophobia, corneal opacity / blue eye d/t anterior uveitis & corneal edema

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98
Q

most commonly recognized infectious cause of acute hepatitis in dogs?

A

leptospirosis (interrogans or kirschneri)

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99
Q

how can you definitively diagnose amanita mushroom ingestion?

A

alpha-amanitin can be detected in liver tissue by liquid chromatography-mass spectrometry

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100
Q

In dogs and cats with hepatic inflammation, what are the 5 most common organisms cultured from bile?

A

E coli, enterococcus, bactericides, streptococcus, clostridium

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101
Q

which copper oxidation state is responsible for most of copper’s hepatotoxicity?

A

cupric (Cu2+)

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102
Q

what does COMMD 1 stand for?

A

copper metabolism gene MURR1- containing domain 1

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103
Q

name two copper-specific stains

A

rubeanic acid &rhodamine

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104
Q

why shouldn’t you give D-penicillamine and zinc concurrently?

A

D-pen will chelate zinc in the blood, reducing its effectiveness

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105
Q

what % of feline liver biopsies reveal inflammatory disease?

A

26% (45 of 175)

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106
Q

what is the most common liver disease in cats?

A

hepatic lipidosis

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107
Q

what is the proposed pathogenesis of neutrophilic cholangitis?

A

ascending intestinal bacterial infection

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108
Q

what is the most common liver enzyme affected in cats with cholantigis?

A

AST (98% have increase); ALT: 50-57% have increase, ALP incr in 14-48%, GGT variable; about 2/3 are hyperbilirubinemic

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109
Q

what test has higher specificity than enzymatic testing for liver dz?

A

pre- and post-prandial bile acids

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110
Q

discuss agreement between cytology & histopathology of feline liver

A

overall 51% agreement. inflammatory dz correctly diagnosed in 27%. vacuolar hepatopathy correctly diagnosed in 83%. Lymphoma may be misdiagnosed as hepatic lipidosis.

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111
Q

what is the most common organism in bile cultures?

A

E coli

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112
Q

What is the most common biochemical abnormality in cats with lymphocytic cholangitis?

A

hypergammaglobulinemia

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113
Q

which has a better prognosis? neutrophilic or lymphocytic cholangitis?

A

lymphocytic (795d versus about 1y)

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114
Q

what % of cats with solitary hepatic abscesses have polymicrobial infection?

A

> 50%

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115
Q

what are the intermediate / paratenic hosts for platynosomum?

A

lizards, terrestrial snails, isopods

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116
Q

what is platynosomum?

A

liver fluke

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117
Q

treatment for platynosomum?

A

praziquantel

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118
Q

when does a cat not shed platynosomum eggs?

A

complete bile duct obstruction

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119
Q

what is the fetal vessel that bypasses the hepatic circulation?

A

ductus venosus

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120
Q

what initiates closure of the ductus venosus?

A

blood pressure changes after umbilical venous flow ceases; thromboxane or various adrenergic compounds stimulate contraction of musculature of ductus venosus & may aid in vessel’s closure

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121
Q

what are the two main trophic hormones for hepatic growth? (i.e. the ones that the liver doesn’t get in a PSS)

A

insulin & glucagon

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122
Q

what toxins are implicated in hepatic encephalopathy?

A

ammonia; decreased alpha-ketoglutaramate; glutamine; aromatic amino acids; SCFA; false neurotransmitters (tyrosine/octopamine, phenylalanine/phenylethylamine, methionine/mercaptans); tryptophan; phenol (from phenylalanine & tyrosine); bile acids; gamma-aminobutyric acid (GABA); endogenous benzodiazepines

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123
Q

what is the proposed mechanism of hepatic encephalopathy for ammonia?

A

increased brain tryptophan & glutamine; decreased ATP availability; increased excitability; increased glycolysis; brain edema; decreased microsomal Na-K-ATPase in brain

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124
Q

what is the proposed mechanism of hepatic encephalopathy for decreased alpha-ketoglutaramate?

A

diversion from Kreb’s cycle for ammonia detoxification; decreased ATP availability

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125
Q

what is the proposed mechanism of hepatic encephalopathy for glutamine?

A

alters blood-brain barrier amino acid transport

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126
Q

what is the proposed mechanism of hepatic encephalopathy for aromatic amino acids?

A

decreased DOPA neurotransmitter synthesis; altered neuroreceptors; increased production of false neurotransmitters

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127
Q

what is the proposed mechanism of hepatic encephalopathy for SCFA?

A

decreased microsomal Na,K-ATPase in brain; uncouples oxidative phosphorylation, impairs oxygen utilization, displaces tryptophan from albumin, increasing free tryptophan

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128
Q

what is the proposed mechanism of hepatic encephalopathy for false neurotransmitters?

A

tyrosine -> octopamine; phenylalanine -> phenylethylamine; methionine -> mercaptans. impair norepinephrine action, synergistic with ammonia & SCFA; decrease ammonia detoxification in brain urea cycle; GIT-derived (fetor hepaticas - breath odor in HE); decreased microsomal Na,K-ATPase

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129
Q

what is the proposed mechanism of hepatic encephalopathy for tryptophan?

A

directly neurotoxic; increases serotonin: Neuroinhibition

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130
Q

what is the proposed mechanism of hepatic encephalopathy for phenol (from phenylalanine & tyrosine)

A

synergistic with other toxins; decreases cellular enzymes; neurotoxic & hepatotoxic

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131
Q

what is the proposed mechanism of hepatic encephalopathy for bile acids?

A

membranocytolytic effects alter cell/membrane permeability; blood-brain barrier more permeable to other HE toxins; impaired cellular metabolism d/t cytotoxicity

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132
Q

what is the proposed mechanism of hepatic encephalopathy for gamma-aminobutyric acid

A

(AKA GABA) neural inhibition: hyperpolarizes neuronal membrane; increase blood-brain barrier permeability to GABA

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133
Q

what is the proposed mechanism of hepatic encephalopathy for endogenous benzodiazepines?

A

neural inhibition: hyper polarize neuronal membrane

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134
Q

what % of hepatic blood & oxygen is provided by the portal vein? where does the rest of it come from?

A

80% of the blood and 50% of the oxygen; rest from hepatic arterial blood

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135
Q

what is the flow of blood through the liver?

A

portal vein -> branches -> venues -> portal triad -> hepatic sinusoids -> reticuloendothelial system -> central veins -> hepatic venues -> hepatic vein -> CVC

136
Q

what are the three most common causes of acquired extra hepatic shunts?

A

hepatic fibrosis/cirrhosis, PVH with portal hypertension, HAVMs

137
Q

what % of cats & dogs with PVH have concurrent congenital macroscopic PSS?

A

58% of dogs, 87% of cats

138
Q

what % of liver function is lost when hepatic encephalopathy occurs?

A

70%

139
Q

top breeds for congenital EHPSS?

A

yorkie, maltese, havanese, dandie dinmont terrier, pug, mini schnauzer

140
Q

what is the odds ratio for Yorkies & PSS?

A

35.9x greater than all other breeds combined

141
Q

why are dogs with PSS PU/PD?

A

poor medullary concentration gradient from low BUN, increased renal blood flow, increased ACTH secretion & associated hypercortisolism, psychogenic polydipsia from HE

142
Q

ascites occurs in what % of dogs with HAVM?

A

75%

143
Q

what % of cats with PSS show ptyalism?

A

75%

144
Q

GI hemorrhage is more common in dogs with IHPSS or EHPSS?

A

IHPSS

145
Q

why do dogs/cats with PSS form ammonium urate calculi?

A

decreased urea production, increased ammonia excretion, decreased uric cid metabolism

146
Q

CNS signs are most frequent with which PSS formation?

A

splenocaval CPSS

147
Q

at what age are most pets diagnosed with HAVM?

A

within the first year of life

148
Q

what % of dogs with HAVM have ascites?

A

75%; we suspect that acquired shunts lead to decompression of the portal system in the remaining 25%

149
Q

what is the typical erythrogram in dogs/cats with PSS?

A

mild to moderate, microcytic, normochromic, non regenerative anemia; target cells in dogs & poikilocytes in cats

150
Q

why do animals with PSS have RBC microcytosis?

A

defective iron-transport mechanism, decreased serum iron concentrations, decreased TIBC, increased hepatic iron stores in Kupffer cells; iron sequestration?

151
Q

what are the typical ALT & ALP in dogs with PSS?

A

increased 2-3x normal; ALP > ALT

152
Q

what serum biochemical changes do you typically find in animals with PSS?

A

low albumin, low BUN, low cholesterol, low BG, high ALT, high ALP, low creatinine

153
Q

what is the theory behind why proteinuria is common in dogs with PSS?

A

glomerulopathy (glomerular sclerosis, glomerulofibrosis, membranoproliferative glomerulonephritis): accumulation of antigens reaching the kidneys that the liver would have otherwise cleared with a normal portal circulation -> immune-med GN

154
Q

what is the basic pathway of bile acids?

A

synthesized in liver from cholesterol -> conjugation -> secreted in bile canaliculi & stored in GB until release into duodenum. aid in lipid absorption via intestinal fat emulsification & metabolism. reabsorbed in ileum -> transported in portal system -> extracted by hepatocytes for recirculation

155
Q

what dog breed can have elevated serum bile acids w/o evidence of hepatocellular dysfunction?

A

maltese

156
Q

what enzyme deficiency in cats can cause hyperammonemia & HE?

A

ornithine transcarbamylase, leading to error in ammonia metabolism in urea cycle

157
Q

describe PT and PTT in patients with acute versus chronic liver disease?

A

chronic - prolonged PTT. acute - prolonged PT & PTT

158
Q

How can plasma protein C activity help differentiate between MVD & PSS?

A

protein C levels are >70% in 88% of dogs with MVD & low in dogs with PSS

159
Q

what electrolyte abnormality can contribute to HE?

A

hypokalemia

160
Q

what acid-base abnormality can contribute to HE?

A

metabolic acidosis

161
Q

why is vegetable protein preferred to animal protein for diets for PSS dogs?

A

vegetable proteins have less aromatic amino acids (tyrosine, phenylalanine) & more branched chain AA (valine, leucine, isoleucine)

162
Q

what are the prognostic indicators for medical management of dogs with CPSS?

A

age at onset of c/s (longer survival for older dogs); BUN (longer survival with higher value)

163
Q

what % of dogs treated medically for a CPSS could be expected to be euthanized w/in 10 mo’s of diagnoses?

A

> 50%

164
Q

what % of dogs with CPSS can survive long term w/medical management alone?

A

33%

165
Q

in anesthesia for dogs with liver disease, what characteristics of drugs should be avoided?

A

avoid anesthetic agents that are highly protein-bound or dependent on liver metabolism

166
Q

what % of EHPSS & what % of IHPSS dogs tolerate complete shunt ligation?

A

EHPSS: 32-52%. IHPSS: <15%

167
Q

symptoms of acute portal hypertension? (such as with complete ligation of a PSS)

A

ascites, intestinal congestion, diarrhea, hypoxemia, bowel death

168
Q

following temporary shunt attenuation, intraoperative portal pressures >XX cm water above resting (preligation) pressures or absolute pressures >XX cm water have been associated with greater postoperative complications

A

> 9-10 cm above resting; >17-24 cm water absolute

169
Q

surgical complication rates are higher with IHPSS or EHPSS?

A

IHPSS

170
Q

what are the more worrisome c/s after a shunt ligation?

A

vomiting, abdominal distension, progressive ascites, abdominal pain, hypotension; can lead to shock and DIC

171
Q

most common long-term complication seen after surgical treatment of PSS?

A

recurrence or persistence of c/s

172
Q

what additional complication do IHPSS dogs have that EHPSS dogs don’t?

A

severe GI ulceration & bleeding

173
Q

how are feline PSS management and canine different?

A

cats have higher preoperative complication rates & worse long-term outcomes

174
Q

what artery to HAVM typically form from?

A

hepatic artery; but have also been reported to involve gastroduodenal artery, left gastric artery, phrenic arteries

175
Q

how common are MAPSS in dogs with HAVM?

A

they have been reported in every dog with HAVM

176
Q

what are the treatments for HAVM?

A

liver lobectomy, ligation of nutrient artery, fluoroscopically-guided glue embolization of abnormal arterial vessels

177
Q

return of bile acids to normal after PSS attenuation is or is not correlated with long-term outcome?

A

is NOT

178
Q

hepatic vascular anomalies: prognostic indicator for medical management alone?

A

age at onset of c/s, BUN

179
Q

most common cause of death after PSS attenuation?

A

severe persistent neuro signs; other causes - intra-op hemorrhage, post-op coagulopathy, portal hypertension, hemorrhagic gastroenteritis

180
Q

dogs undergoing surgery for EHPSS: prognostic indicators?

A

hypoalbuminemia (in dogs undergoing aneroid constrictor placement) = more likely to have persistent post-op shunting. other factors: pre-op hypoalbuminemia, leukocytosis, seizures after surgery, persistent shunting 6-10 wks after surgery = poor long-term prognosis

181
Q

MST for IHPSS?

A

1-3 years. post-op complications as high as 77% w/surgery, short-term mortality 11-28%. overall mortality 23-64%.

182
Q

IHPSS: prognostic indicators

A

better short-term outcomes: body weight >10kg, total protein >4g/dL, albumin >2.6 g/dL, BUN >7.4g/dL. better long-term survival w/higher PCV & TP. Poorer long-term outcome w/pre-op hypoalbuminemia or leukocytosis, seizures after sx, persistent shunting 6-10 wks after sx. Note: post-op serum bile acids have NOT been associated with survival

183
Q

MVD/PVH: survival %?

A

92% have had good long-term survival

184
Q

most common post-op complications in cats undergoing sx for PSS?

A

neuro dysfunction, including generalized seizures & central blindness, which can resolve a few months after surgery

185
Q

what is the most common predominantly secondary metabolic hepatopathy in small animals?

A

vacuolar hepatopathies

186
Q

define vacuolar hepatopathies

A

a condition in which hepatocytes become loaded with fat (steatosis) or glycogen or water (hepatocellular swelling, or cloudy swelling); lysosomal storage diseases can also lead to hepatocyte vacuolation

187
Q

what causes cloudy swelling? what are the consequences?

A

occurs when hepatocytes are injured & less able to maintain fluid homeostasis; if swelling is severe & chronic, it can cause hepatocyte death, fibrosis, and cirrhosis

188
Q

severe congenital cobalamin deficiency has been reported to cause what liver change(s) in dogs? why do we think this occurs?

A

foamy vacuolation of hepatocytes, lipogranulomas, single cell necrosis, & mild fibrosis; possibly due to secondary hyperhomocysteinemia

189
Q

vacuolar hepatopathy can lead to what cancer in what breed? what lab work change do you see associated with this?

A

HCC in scottish terriers. increased ALP

190
Q

what vitamin deficiency can lead to steroid hepatopathy & cloudy changes in dogs?

A

cobalamin deficiency

191
Q

what endocrine diseases in cats & dogs can lead to steatosis?

A

dogs: hypothyroidism, DM. cats: hyperthyroidism

192
Q

name two toxic causes of vacuolar hepatopathies

A

aflatoxin (dogs), vitamin A (cats)

193
Q

describe the process of steroid hepatopathy development

A

hepatocytes become vacuolated with marked cytoplasmic, or even nuclear, increases in glycogen. vacuolation starts in the centrilobular region (zone 3) & become generalized when chronic

194
Q

why do dogs get an increase in ALP with steroid hepatopathy?

A

could be a result of delayed clearance of the intestinal isoenzyme d/t hyperglycosylation in the liver under the influence of GCC

195
Q

what is the treatment for steroid hepatopathy?

A

remove the source of exogenous/endogenous GCC. if that isn’t possible, antioxidants (SAMe increases hepatic glutathione & had beneficial effect on oxidized:total glutathione ratio in hepatocytes)

196
Q

what is the typical signalment of a scottie with idiopathic vacuolar hepatopathy?

A

middle-aged (median 8y, although dogs with HCC are older); no gender predilection

197
Q

describe lab work abnormalities & c/s in scotties with idiopathic vacuolar hepatopathy?

A

moderate to marked elevation in ALP and milder increase in ALT; nearly half show c/s suggestive of hyperadrenocorticism, but ACTH stim & LDDST are variable

198
Q

what are the most consistent endocrine abnormalities in scotties with idiopathic vacuolar hepatopathy?

A

increases in progesterone & androstenedione post-ACTH stimulation

199
Q

what is the difference between macrovesicular and microvesicular steatosis?

A

micro vesicular - multiple vacuoles that are smaller than the cell nucleus, typical in DM in dogs. macro vesicular - larger vacuoles, which often displace nucleus to periphery of cell. Feline hepatic lipidosis is assoc w/both micro & macro

200
Q

aflatoxicosis causes what metabolic change in the liver?

A

steatosis (as a result of hepatocyte injury)

201
Q

what changes occur to the liver cells in chronic vitamin A intoxication in cats?

A

hypertrophy of lipid-laden hepatic stellate cells, with or without hepatocellular steatosis & fibrosis

202
Q

what metabolic change can be seen in livers of dogs with congenital PSS?

A

steatosis

203
Q

name 3 predisposing factors for feline hepatic lipidosis

A

obesity, anorexia, stress

204
Q

how much weight do cats have to lose to develop feline hepatic lipidosis?

A

25? in one study, 30-40% in another

205
Q

describe the proposed pathophys of feline hepatic lipidosis

A

fasting + stress = increase in peripheral lipolysis -> bottleneck effect in liver, such that mobilized lipids become trapped, with reduced export. marked steatosis of hepatocytes interferes with metabolic activity of cells and produces a secondary cholestasis d/t compression of small intrahepatic cholangioles. this leads to acute liver failure.

it has also been proposed that protein deficiency and negative nitrogen balance assoc w/fasting reduce ability to produce apoproteins to export fat from liver, and that taurine and carnitine deficiencies contribute to pathogenesis (but these have limited support w/research)

206
Q

describe lipid levels in cats with hepatic lipidosis

A

elevated circulating triglycerides and NEFA, consistent with lipolysis of peripheral fat & reduced function of HSL; they can also have higher serum beta-hydroxybutyrate than normal cats, indicating hepatic ketogenesis; can still mobilize triglycerides form liver - significant increase in serum VLDL. it’s proposed that they can’t remove triglycerides fast enough to compensate for increased mobilization

207
Q

insulin in cats with hepatic lipidosis is increased or decreased

A

normal or reduced (suggesting that affected cats are not insulin-resistant)

208
Q

adiponectin and leptin are high or low in cats with hepatic lipidosis

A

both are high. high leptin should lead to reduction of lipid content of non-adipose tissues like liver, so affected cats must be leptin-resistant

209
Q

what is the typical signalment of a cat with hepatic lipidosis

A

younger to middle-aged female cat. idiopathic cases tend to be younger than secondary cases

210
Q

how do you diagnose hepatic lipidosis?

A

biopsy

211
Q

what are the typical biochem changes in cats with hepatic lipidosis?

A

marked increase in bilirubin, ALP, ALT; normal GGT (although cat with secondary FHL can have very elevated GGT if there is concurrent biliary stasis). hypokalemia d/t anorexia and vomiting. hyperglycemia

212
Q

what proportion of cats with hepatic lipidosis have prolonged coagulation times

A

about half; clinically significant bleeding is rarely reported

213
Q

what is the most important factor affecting prognosis in cats with hepatic lipidosis?

A

early intensive feeding (primary and secondary FHL)

214
Q

what type of diet is most effective at reducing hepatic lipid?

A

high protein diet

215
Q

what vitamin should be measured in cats with hepatic lipidosis?

A

cobalamin

216
Q

some cats with hepatic lipidosis develop hepatic encephalopathy. what is the feeding recommendation in this case?

A

NOT low protein diet, but instead reduce the amount fed - feed in small frequent meals and institute therapies for any concurrent inflammatory disease

217
Q

superficial necrolytic dermatitis has been associated with what drug?

A

phenobarbital

218
Q

superficial necrolytic dermatitis has been associated with what 2 neoplasms?

A

glucagonoma, insulinoma

219
Q

describe the pathogenesis of skin lesions associated with superficial necrolytic dermatitis

A

amino acid deficiency; zinc and fatty acid deficiencies also implicated. these are proposed to be d/t unregulated hepatic metabolic activity under stimulus of increased glucagon activity, or to unidentified stimulus

220
Q

describe the typical signalment of a dog with superficial necrolytic dermatitis

A

older small-breed dog. 75% male; mean/median 10yo (range 5-15y)

221
Q

describe the skin lesions of superficial necrolytic dermatitis

A

hyperkeratotic erythematous crusting; on extremities (paw pads, nose, periorbital, perianal), around genitals, pressure points. lesions develop fissures and bacterial infection, painful

222
Q

what % of dogs with superficial necrolytic dermatitis have diabetes mellitus?

A

25-40%

223
Q

describe histopathology of skin biopsies for superficial necrolytic dermatitis

A

parakeratotic hyperkeratosis with inter- and intra-cellular edema = red, white, and blue on H and E staining

224
Q

what disease has the same skin histopath lesions as superficial necrolytic dermatitis?

A

zinc responsive dermatosis

225
Q

describe the treatment for superficial necrolytic dermatitis

A

supportive care - amino acids, NOT hepatic diet. high-quality, digestible, high-protein diet like those designed for GI dz or convalescence. supplementation with Zn and EFA, egg yolks, antibiotics for skin +/- shampoo, analgesia; avoid steroids

226
Q

what is hemochromatosis?

A

iron overload in the liver

227
Q

why does secondary hemochromatosis develop?

A

iron is not excreted in bile. 2ndary dz will occur if there is increased absorption in intestine, abnormal excretion, or increased hepatic storage secondary to red cell hemolysis

228
Q

in hemochromatosis, describe liver lesions

A

loading of macrophages & Kupffer cells with hemosiderin, hepatocellular degeneration, periportal fibrosis leading to bridging fibrosis and cirrhosis

229
Q

how do dogs develop secondary hemochromatosis?

A

dietary iron overload, hemolytic anemia d/t pyruvate kinase deficiency, repeated therapeutic blood transfusions

230
Q

what is alpha-1 anti-trypsin?

A

neutrophil elastase manufactured in liver

231
Q

discuss the 3 forms of alpha-1 anti-trypsin in dogs

A

fast, intermediate, slow. intermediate - most common in Cockers with chronic hepatitis

232
Q

what is fecal alpha-1 anti-trypsin used for?

A

detecting protein-losing enteropathy

233
Q

what is serum amyloid a?

A

acute phase protein made by hepatocytes. its transcription is regulated by cytokines. it is the most common form of amyloid in small animals; usually occurs secondary to inflammatory disease

234
Q

what APP(s) is/are produced in largest amount(s) in the face of inflammation?

A

SAA & CRP

235
Q

describe amyloid AL

A

monoclonal IgG light chain. amyloidosis d/t amyloid AL is rare in small animals, but has been described in association with tracheal disease and extra medullary plasmacytoma in dogs and cats. liver involvement is not important with amyloid AL

236
Q

hepatic amyloidosis is most common in which species

A

cats

237
Q

describe amyloidosis in cats

A

most commonly familial and systemic (associated with SAA), but can be sporadic. in abyssinians, it usually presents as CKD, with renal medulla involved more than glomeruli. siamese often have hepatic involvement.

238
Q

why do cats with hepatic amyloidosis most often present?

A

acute intra-abdominal bleeding from fracture of a fixable liver

239
Q

describe the typical clfinicopathologic findings in cats with hepatic amyloidosis

A

high ALT, globulins, bilirubin; anemia; biliary enzymes rarely increased. may see signs of chronic inflammatory dz / comorbidities

240
Q

if you were to treat a dog with hepatic amyloidosis, what would you use?

A

colchicine

241
Q

what are the predominant c/s of lysosomal storage diseases?

A

neurological & skeletal > hepatic

242
Q

what is the predominant c/s in lipid storage disease (cholesterol ester storage disease)

A

hepatosplenomegaly d/t accumulation of lipid and cholesterol crystals in liver and spleen

243
Q

what are the two major causes of drug-induced hepatotoxicosis?

A

cytotoxic & cholestasis

244
Q

describe the cytotoxic category of drug-induced hepatotoxicosis

A

due to hepatocyte toxicosis from parent compound or a locally generated metabolite; leads to a hepatocellular pattern of liver injury d/t hepatocyte necrosis

245
Q

describe the cholestatic category of drug-induced hepatotoxicosis

A

can occur when compounds inhibit or down regulate transporter pumps in sinusoidal or canalicular membranes, thus interfering with bile salt efflux & hepatocyte functions. cholestatic pattern can also result from mitochondrial injury leading to steatosis

246
Q

list 14 drugs involved in dosage-dependent hepatotoxicosis

A

acetaminophen, aflatoxin, amanita mushrooms, amiodarone (dog), azathioprine (d), azoles, CCNU (d), cycads (d), glipizide (cat), phenazopyridine (rhabdomyolysis predominates), phenobarbital (d), phenytoin (d), primidone (d), xylitol (d)

247
Q

what are the 4 mechanisms of dose-dependent hepatotoxicity?

A

oxidative stress, mitochondrial dysfunction, transporter dysfunction, p450 induction

248
Q

describe the “transporter dysfunction” mechanism of dose-dependent hepatotoxicity & give 2 examples

A

drugs can inhibit or down regulate transporter pumps and lead to a functional cholestasis. Ex) cholestasis of pregnancy (endogenous hormone metabolites), endotoxin

249
Q

describe the “oxidative stress” mechanism of dose-dependent hepatotoxicity & give 3 examples

A

metabolites cause oxidative stress; antioxidant supplementation may be effective for treatment/prevention of liver toxicosis. ex) acetaminophen, azathioprine, azole antifungals

250
Q

describe the “mitochondrial dysfunction” mechanism of dose-dependent hepatotoxicity & give 2 examples

A

drugs interfere with mitochondrial function and can lead to steatosis from inhibition of fatty acid beta-oxidation, or can lead to more severe hepatocellular damage due to impaired cellular respiration. ex) tetracyclines, amiodarone

251
Q

describe the “P450 induction” mechanism of dose-dependent hepatotoxicity & give 2 examples

A

drugs act as P450 inducers and lead to hepatotoxicosis by chronic bioactivation of environmental toxins. ex) phenobarbital, phenytoin

252
Q

describe the theory behind idiosyncratic hepatotoxicity

A

caused by reactive metabolites that are variably generated among individuals. these metabolites may cause oxidative stress, mitochondrial damage, or lead to formation of haptens that trigger a humoral or T cell-mediated immunologic response. they may or may not involve an adaptive immune response. metabolites may bind to critical proteins and impair hepatocyte function, or generate ROS that damage hepatocyte membranes. drug-protein adducts can be processed and presented to immune system with MHC molecules, which leads to clonal expansion of drug-specific T cells +/- generation of drug-specific antibodies that target hepatocyte proteins. usually requires discontinuation of suspect drug & structurally related drugs.

253
Q

List 6 drugs associated with idiosyncratic hepatotoxicity

A

carprofen (d), diazepam (c), mitotane (d), potentiated sulfonamides (d), zonisamide (d)

254
Q

in idiosyncratic hepatotoxicityy, how are reactive metabolites generated?

A

locally in the liver by cytochrome p450s (CYPs), flavin mono-oxygenates (FMOs), or other pathways

255
Q

name two drugs that are associated with idiosyncratic hepatotoxicity via oxidative stress

A

methimazole and (possibly) diazepam

256
Q

name three drugs that are associated with idiosyncratic hepatotoxicity via drug happen formation with immune response

A

potentiated sulfonamides, (possibly) felbamate, and (possibly) zonisamide

257
Q

high doses of acetaminophen cause what toxicities?

A

acute centrilobular hepatic necrosis; cats also get hematologic toxicosis - methemoglobinemia and cyanosis

258
Q

why are cats more susceptible to acetaminophen toxicity?

A

absent expression of UGT1A6, the enzyme that glucuronidates acetaminophen, and possibly also due to decreased expression of ABCG2 transporter, which exports acetaminophen sulfate in humans

259
Q

why do we treat acetaminophen toxicity with NAC?

A

acetaminophen is bioactivated to the reactive metabolite, NPQI (N-acetyl-p-benzoquinone imine), which is detoxified by glutathione conjugation. NAC is a glutathione precursor.

260
Q

for animals with methemoglobinemia from acetaminophen intoxication, what drug can be used to restore functional hemoglobin?

A

ascorbate (vitamin C) (efficacy not evaluated)

261
Q

what is the proposed mechanism of phenobarbital hepatotoxicity?

A

induction of cytochrome P450 enzymes, which secondary bioactivation and hepatotoxicity of other drugs, dietary components, or environmental toxins.

262
Q

describe phenobarbital hepatotoxicity in cats

A

phenobarbital does not lead to enzyme induction or hepatotoxicosis in cats

263
Q

discuss the mechanism of ketoconazole hepatotoxicity

A

oxidative metabolite (N-deacetyl ketoconazole) leads to covalent binding to liver proteins and glutathione depletion; so co-treatment with glutathione precursors like SAM-e can be considered if dogs get increased liver enzymes during treatment

264
Q

discuss the mechanism of azathioprine hepatotoxicity

A

generation of oxidative metabolites and depletion of hepatic antioxidants; can be prevented by pre-treatment with NAC. oxidative metabolites of azathioprine are generated by xanthine oxidase

265
Q

what breed seems to be more at risk for azathioprine hepatototixcosis?

A

GSD

266
Q

describe the clin path changes seen with amiodarone toxicity

A

increases in ALT +/- hyperbilirubinemia, +/- neutropenia

267
Q

discuss the mechanism of amiodarone hepatotoxicity

A

two oxidative metabolites: mono-N-desethylamiodarone (MDEA), and di-N-desethylamiodarone (DDEA), which generate ROS that uncouple oxidative phosphorylation and lead to mitochondrial damage. these metabolites are generated by CYP3A4 in humans, and their generation can be inhibited by ketoconazole in vitro

268
Q

what breed is most prone to hepatotoxicosis with CCNU? what age?

A

boxers; younger dogs (<5yo)

269
Q

what should be given concurrently with CCNU in all treated dogs?

A

denamarin (silybin + SAM-e)

270
Q

discuss the mechanism of tetracycline hepatotoxicity

A

inhibition of beta-oxidation of fatty acids in hepatic mitochondria, as well as inhibition of hepatic lipoprotein secretion. although tetracycline inhibits fatty acid beta-oxidation in vitro, there is no histologic evidence for steatosis from tetra/doxycycline use in dogs

271
Q

describe clin path changes associated with potentiated sulfonamide hepatotoxicity

A

hepatocellular pattern progresses over several days to cholestatic

272
Q

what is the most common histologic finding seen with potentiated sulfonamide hepatotoxicity

A

hepatic necrosis

273
Q

list ADE for potentiated sulfonamides

A

hepatic necrosis, fever, neutropenia, thrombocytopenia, hemolytic anemia, polyarthropathy, proteinuria, KCS, skin lesions, uveitis

274
Q

discuss the mechanism of potentiated sulfonamide hepatotoxicity

A

oxidized to form nitroso metabolite that covalently bind to proteins and act as haptens

275
Q

discuss the mechanism of methimazole hepatotoxicity

A

incr ALT, dose-dependent centrilobular hepatic necrosis, glutathione depletion. oxidative metabolite, N-methylthiourea, is generated by flavin mono-oxygenates

276
Q

aflatoxins are produced by what species?

A

aspergillus

277
Q

where can aflatoxins be found?

A

moldy corn, peanuts, or soy; contaminated pet food; wild bird seed

278
Q

describe the mechanism of aflatoxin hepatotoxicosis

A

aflatoxin B1 is a dose-dependent hepatotoxin. it is bioactivated by cytochrome P450 enzymes to electrophilic epoxide metabolites that lead to protein and DNA adducts and glutathione depletion

279
Q

describe clin path change seen in aflatoxin hepatotoxicosis

A

decreases in serum protein C, antithrombin, and cholesterol are more sensitive than increases in liver enzymes or bilirubin early in course of disease; hyperbilirubinemia, hypoalbuminemia, and hypocholesterolemia are poor prognostic indicators.

280
Q

what is unique about aflatoxin hepatotoxicosis in dogs, histologically speaking?

A

massive hepatic necrosis is NOT a feature. rather, you see diffuse hepatocyte lipid vacuolation, fibrosis, biliary hyperplasia +/- cirrhosis

281
Q

how can you test for aflatoxin toxicosis?

A

submit food for aflatoxin B1 analysis; vomitus, serum, and urine can be analyzed for M1 metabolite of aflatoxin B1

282
Q

describe the progression of toxicosis from xylitol

A

30-60 minutes: insulin release and hypoglycemia. 6-72 hours: acute hepatic necrosis, sometimes leading to consumptive coagulopathy and fulminant liver failure

283
Q

describe the mechanism of amanita mushroom hepatotoxicosis

A

amatoxins, especially alpha-amanitin, inhibit RNA polymerases, leading to decreased mRNA generation, arrested protein synthesis, and necrosis of metabolically active cells, including intestinal rapt cells, hepatocytes, and renal tubular cells

284
Q

describe the clinical course of toxicosis from amanita

A

vomiting/hematochezia/abodminal pain 6-24 hours after ingestion. hypoglycemia 24-48h d/t insulin release stimulated by alpha-amanitin. massive hepatic necrosis and renal tubular necrosis develop after 36-84 hours

285
Q

what drug can be used in amanita toxicosis?

A

silybin (from milk thistle) inhibits amatoxin uptake by hepatocytes, which is mediated by OATP1B3 transporter

286
Q

how can you diagnose amanita toxicosis

A

measure alpha-amanitin in urine, serum or plasma, kidney, or liver

287
Q

what genera of blue-green algae cause hepatotoxicosis?

A

microcystis aeruginosa (freshwater lakes, ponds, reservoirs) and nodularia spumigena (brackish and ocean waters)

288
Q

discuss the mechanism of blue-green algae hepatotoxicosis

A

cyanotoxins microcystin and nodular inhibit serine/threonine protein phosphates in the liver, with subsequent hyperphosphorylation and disruption of cytoskeletal proteins. this leads to hepatocyte dissociation, hepatic necrosis, and glutathione depletion

289
Q

nodularin can cause disease in what organ other than the liver?

A

kidney: proximal renal tubular necrosis and anuric kidney injury

290
Q

how can you diagnose blue-green algae toxicosis?

A

cytology of vomitus; toxicologic analysis of water, vomitus, feces, or liver for nodularin or microcystin

291
Q

what drug should be given with blue-green algae toxicosis and why?

A

cholestyramine - binds cyanotoxins in gut

292
Q

discuss the mechanism of cycad palm hepatotoxicity

A

cycasin is bioactivated to methylazoxymethanol by gut bacteria; this metabolite leads to GI and hepatic toxicosis. neurologic signs are seen, too

293
Q

primary hepatic tumors are what % of all tumors in dogs?

A

0.6-1.5%

294
Q

primary liver tumors are what % of all tumors in cats?

A

1-3%

295
Q

how much more common are metastatic tumors than primary liver tumors in dogs?

A

3x

296
Q

are primary or metastatic liver tumors more common in cats?

A

primary

297
Q

most common liver tumor in dog?

A

HCC

298
Q

what is the most common primary eline hepatobiliary tumor?

A

bile duct adenoma

299
Q

which lobes are affected most commonly in HCC?

A

left lateral and medial and the caudate lobe

300
Q

if a HCC metastasizes, which places are most likely? what is the met rate?

A

regional LNN, peritoneum, lungs. for massive HCC - 0-37%; for nodular/diffuse - 93-100%

301
Q

what breed & gender are predisposed to canine bile duct tumor?

A

labrador retriever; female

302
Q

describe biologic behavior of primary hepatic neuroendocrine tumors

A

aggressive, usually not surgically resectable due to diffuse nature; metastasize to regional LNN, peritoneum, lungs&raquo_space; heart, spleen, kidney, adrenal glands, pancreas

303
Q

how good is RT for liver tumors?

A

bad. liver is very sensitive to low radiation, and there’s difficulty limiting tissue exposure

304
Q

in general HCC is chemo-resistant. what two drugs have shown to maybe have some effect in dogs?

A

gemcitabine & mitoxantrone

305
Q

treatment: bile duct carcinoma

A

none

306
Q

prognostic factors for dogs with massive HCC?

A

tumor location, serum ALT and AST, ratio of ALP to AST and ALT to AST, histopathologic subtype and anapestic characteristics

307
Q

MST of dogs with massive HCC managed by liver lobectomy versus conservative therapy?

A

sx: not reached after 1460 days of follow-up. medical: 270d

308
Q

prognosis for cats with surgically resectable bile duct adenoma?

A

excellent - no reports of local recurrence or malignant transformation

309
Q

what is the path that bile takes to get into the GB?

A

formed in hepatocytes. actively secreted into bile acnaliculi. then into interlobular ducts and ultimately lobar ducts. lobar ducts give rise to left and right hepatic ducts. cystic duct is offshoot of hepatic ducts and travels towards GB

310
Q

what is bile made of?

A

cholesterol, lecithin, phospholipids, bile salts

311
Q

what is the purpose of bile?

A

emulsify fat and neutralize acid in partially digested food

312
Q

what is the difference between dog & cat bile tract anatomy?

A

dog: CBD joins minor pancreatic duct and both exit separately at major duodenal papillae. cat: CBD fuses with major pancreatic duct before entering the duodenum

313
Q

what signalment is predisposed to choleliths?

A

old, female dogs. mini schnauzer & mini poodle

314
Q

describe the physiology behind cholelith formation

A

cholesterol is strongly hydrophobic, necessitating transport in micelles to remain suspended in solution. when an imbalance occurs between bile salts and cholesterol, bile becomes more viscous leading to formation of gallstones.

315
Q

what predisposes a patient to developing choleliths?

A

gallbladder dyskinesia, hypercholesterolemia, hypertriglyceridemia, hyperbilirubinemia, endocrine disease, cholesterol absorption and transport defects in GB

316
Q

in cats, a CBD diameter greater than X mm is indicative of extra hepatic biliary obstruction

A

5mm

317
Q

what factors predispose an animal to cholecystitis?

A

bile stasis, GB mucocele, ascending bacterial or parasitic diseases, biliary neoplasia, infarction, hematogenous spread of bacteria. in cats, bacterial infections are thought to be secondary to inflammation rather than the inciting factor.

318
Q

what characteristic of abdominal effusion allows you to diagnose it as biliary rupture?

A

bilirubin in effusion is > 2x that in circulating blood

319
Q

in cats, a GB wall thickness of > x mm predicts GB dz

A

1mm

320
Q

what are the most common isolates in cholecystitis?

A

E coli, enterococcus, bactericides, streptococcus, clostridium, helicobacter

321
Q

emphysematous cholecystitis has been associated with which diseases?

A

diabetes mellitus

322
Q

what is the most appropriate treatment for emphysematous cholecystitis?

A

surgical intervention

323
Q

what bacteria are most commonly isolated in emphysematous cholecystitis?

A

anaerobes, E coli, clostridium perfringens

324
Q

which antibiotics are best for empirical use in cholecystitis?

A

fluoroquinolones, metronidazole, chloramphenicol - high concentrations in bile, strong anaerobic activity

325
Q

discuss pathogenicity of biliary cystadenomas

A

rarely make a problem; may need to be surgically resected if space-occupying problems arise. favorable prognosis

326
Q

name 3 species of flukes that infect feline biliary tract & liver

A

platynosomum fastosum, platynosomum concinnum, amphimerus pseudofelineus

327
Q

describe the life cycle of hepatobiliary flukes

A

ova of flukes passed in cat feces. land snail ingests ova. amphibian or reptile (toad, gecko, lizard) eats the snail. cat eats the second intermediate host.

328
Q

are cats always symptomatic for hepatobiliary flukes?

A

no, some arasymptomatic carriers

329
Q

what is the most reliable method of diagnosing hepatobiliary parasites?

A

fecal sediment; aspiration & cytology of bile are useful for ID’ing fluke eggs if fecal is negative

330
Q

treatment for biliary flukes?

A

praziquantel; consider steroids & antihistamines prior to treatment to control inflammatory response. surgery if biliary obstruction. abx if neutrophilic cholangitis on histopath

331
Q

list the predisposing factors for a biliary mucocele

A

dyslipidemia, dysmotility of GB, endocrine disease, exogenous steroid administration. sheltie, cocker, mini schnauzer. in cats, biliary stasis and congenital biliary abnormalities are thought to play a role.

332
Q

why do steroids cause an increased risk of mucocele?

A

high dose steroids lead to higher unconjugated bile acids within extra hepatic biliary tree. unconjugated bile acids are more hydrophobic and when in disproportionate levels, lead to injury of biliary epithelium. ucin secretion increases as a result of the injury and ultimately leads to mutinous hyperplasia

333
Q

how does hypothyroidism predispose animals to GB mucocele formation?

A

reduced bile flow; sphincter of Oddi relaxation impaired, liver cholesterol metabolism altered and bile secretion diminishes. mucin organizes and solidifies under these conditions.

334
Q

shelties treated with this drug are more likely to develop a mucocele

A

imidacloprid (in flea control products)

335
Q

what liver enzyme is predominantly elevated in GB mucoceles?

A

ALP

336
Q

what bacterial organisms are most commonly found in patients with mucoceles?

A

enterococcus, enterobacter, E coli, staph, strep

337
Q

what type of diet should be given to a patient undergoing medical therapy for a mucocele?

A

low fat

Ettinger Notes (2 decks)

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