Hepatobiliary Disease of the Dog and Cat

What is the a second largest organ in the body?

liver

What are some of the functions of the livers? (6)

Synthesis, detoxification, vitamin storage and activation, hormone

deactivation and excretion, bile salt synthesis, processing of bilirubin

How do you bleed if the there is a messed up liver?

clotting factor bleeding disease- massive bleeds everywhere

T/F Liver has 80% reserve capacity and the ability to regenerate

True

Why is the majority of liver disease subclinical?

due to the fact that the liver has regenerative ability

What age of dogs do you commonly see in Congenital PVA?

younger dogs

What is the signalment do you assume a dog with Lobar dissecting hepatitis?

Dogs <1 yr with ascites

What is the signalment for Hepatitis is very common?

female dobermans

What vaccine is very important for the liver and why?

CAV-1, it is the cause of viral acute hepatitis

What does acholic feces means and why does this happen?

pale stool, it lacks the bile pigmentation could be due to a bile duct obstruction

Elevations in ALT for longer than how many weeks warrants an investigation

6

T/F Extrahepatic disease can result in enzyme elevations

True

What type of enzymes stored in the cytosol and "leak" out of the cell with membrane damage (e.g., inflammation, necrosis)?

Leakage enzymes

What are the TWO Leakage enzymes?

ALT, AST

T/F Liver enzymes tell you about liver function

False, liver integrity`

Which leakage enzyme is liver specific?

ALT

Which leakage enzyme is associated with liver, skeletal and cardiac muscle, red blood cells?

AST

Where is AST found?

found in the cells mitochondria

What enzyme is being describe below:

Markers of hepatocellular damage

• Within the cytoplasm and mitochondria

• A marker of hepatocellular injury

• Does not predict reversibility

• Increased is proportionate to degree of injury/mass of affected

tissue

• The more severe the injury, generally the less reversible it is

• Pretty liver-specific (small amount in the muscle)

ALT

What do increase of ALT up to 2 fold mean with regards to recheck?

can be rechecked at 2-week intervals for up to 6 weeks and possibly treated with nutraceutical hepatoprotectants

What is the range that require more of a diagnostic workup that may include measurement of bile acids or ammonia as well

as leptospirosis serology and/or polymerase chain reaction?

Two- to 5-fold increases

T/F For increases greater than 5-fold, an immediate diagnostic workup is recommended

TRue

Which animal is it more significant that there is an increase of liver enzymes and why?

cats, due to the shorter half life

AST:

Hepatocellular; significant muscle and rbc quantities - considered less liver specific

Half-life of approximately __ hours in dogs and __ hours in cats

12 hours, 1.5 hours

What are the TWO liver enzymes that are markers of cholestasis or enzyme induction?

ALP, GGT

T/F ALP is membrane bound (bile duct canaliculi) and "induced" in dogs

only by several drugs

True

Serum half-life of liver ALP is approximately __ hours in the dog and __ hours in the cat

70, 6

Which of the inducible liver enzymes is a sensitive marker of cholestasis?

ALP

The shorter half-life in ___ means that increases in ALP are generally not as high as in ___

cats, dogs

T/F Increases in the cat are more significant than in the dog because of the significantly shorter half-life

True

If there is increases of GGT, what would you expect to be happening?

cholestasis or biliary hyperplasia

If the ALT/AST is significantly higher than ALP/GGT, there is evidence of liver failure and hyperbilirubinemia, what do you think is happening?

Hepatocellular injury

If ALP/GGT is significantly higher than ALT/AST, ± Hypercholestolemia, ± Hyperbilirubinemia, what do you think is occuring?

Cholestasis

If there is • ALT and ALP comparable

• ± Evidence of liver failure

• As above for cholestasis/injury, what do you think is occuring?

mixed

T/F Elevation of liver enzymes do not provide an evaluation of liver function and is no correlation between the magnitude of

enzyme elevation and the capacity of the liver to function

True

WHat are the FOUR Liver "pseudo-function" tests?

1. ↓ Albumin

2. ↓ BUN

3. ↓ Glucose

4. ↓ Cholesterol

Pseudo-function" because the are impacted by other diseases. All of these (do/do not) have to be simultaneously altered

do not

What are the THREE test that directly test liver function?

1. Total bilirubin

2. Bile acids

3. Ammonia

What is an additional diagnostic test that can be used to for liver function?

coagulation

What is caused by retention of bilirubin in the tissues?

icterus

What are the THREE ways to classify Hyperbilirubinemia?

Prehepatic, Hepatic, Post-Hepatic

What are the TWO causes of pre-hepatic hyperbilirubinemia?

• Overproduction

• Impaired uptake (sepsis)

What are the TWO causes of hepatic hyperbilirubinemia?

• Impaired uptake/metabolism

• Impaired excretion

What is the main cause of post hepatic hyperbilirubinemia?

• Impaired excretion

How would you diagnose prehepatic hyperbilirubinemia and how does the animal present?

• Anemia with normal TP

• Evidence of destruction

• Dx: CBC

How would you diagnose hepatic hyperbilirubinemia and how does the animal present?

• Hepatocellular injury

• Mixed pattern

• Dx: enzymes/function/imaging

How would you diagnose post hepatic hyperbilirubinemia and how does the animal present?

• Cholestatic pattern

• Mixed pattern

• Dx: imaging

What is synthesized from cholesterol in the liver?

bile acids

What are bile acids conjugated into?

glycine or taurine

T/F Bile acids under go a mid enterohepatic circulation

False, Undergoes VERY efficient enterohepatic circulation

What are the FOUR testing requirements for Bile Acids?

• Fasted for 12 hours

• Only in non-hyperbilirubinemic patients

Unless basal BA are elevated, post prandial BA should be run (2 hrs after a small meal)

• You need to assess the livers capacity to capture BA as they

recirculate

What are the SIX things that can affect the Pre- and Post-prandial BA?

• Completeness of GB emptying

• Rate of gastric emptying

• Intestinal transit

• Lipemia (false increase)

• Hemolysis (false decrease)

• Efficiency of ileal reabsorption

What substance is produced in the gut by bacteria and enterocytes as a breakdown

product of diet protein?

Ammonia

How much of the liver must be gone to show

serum ammonia concentration to be increased?

greater than 70%

T/F Plasma ammonia concentrations are not influenced by cholestasis or hepatic disorders that do not alter the portosystemic circulation or significantly reduce hepatic functional mass

True

If there is a high resting ammonia, what do you suspect is happening?

Marker of hepatic encephalopathy particularly in the presence of neurologic disease

T/F Normal NH3 does rule out liver disease

False, does not

If you are getting a resting ammonia, what is requires for a liable sample?

Requires a 12 hours fast and a good lab

When do you do a Ammonia tolerance test?

If resting NH3 is normal and hepatic failure is still suspected

What is required for an ammonia tolerance test?

Requires a baseline fast and administration of NH4Cl2 (oral or rectal)

What on a CBC can show you if there are some concerns with the liver?

• Anemia: bleeding

• Erythrocyte morphology: acanthocytes,

target cells, microcytosis (PSS)

• Thrombocytes: mild-moderate

thrombocytopenia

If there is a urinalysis done on a PU/PD pt, wha would you expect to see if there IS liver disease?

isosthenuria to minimally

concentration

What would you expect to see in cats that reflects hepatic disease?

Bilirubinuria

What type of crystals are seen with with portosystemic vascular anomalies?

Ammonium biurate crystals

What is the best imaging modality for diagnosis of liver disease?

ultrasound (also rads)

What type of vitamin dependent activation occurs in the liver? What are the factors?

Vitamin K- II, VII, X, XI protein C and protein S

What is the shortest acting Vit K activation fator?

VII

What drug commonly affects the Vit K activation factors?

warfarin

If you liver is f***, then what occurs to coagulation

hypocoagulable, hypercoagulable, and/or hyperfibrinolytic states can emerge, leading to an increased propensity to bleed or clot

What MUST be done invasive procedures in animals with liver disease?

Tests that evaluate coagulation

What are the min requirement for coagulation test?

platelet count, PT and PTT

What are disease of the liver <2 weeks in duration without previous evidence of hepatobiliary disease?

acute hepatic disease

Acute hepatocyte death from several etiologies, what are the TWO most common?

apoptosis and

necrosis (most common in liver failure)

What are FIVE parasitic causes of acute hepatic disease?

• Parasitic

• Visceral larval migrans

• Heterobilharzia

• Dirofilaria immitis

• Live flukes

What are the FIVE toxins that causes acute hepatic disease?

alflatoxins, amanita mushrooms, blue green algae, cyccad palms, xylitol

What are the drugs that can cause acute hepatic disease?

What are the infectious causes of hepatic disease?

What is needed to onfirm presence of necrosis?

liver biopsy

What, with regards to history, should set off bells that it may be acute hepatic disease?

if there is a sudden onset

What can you give for liver support?

Antioxidants/Cytoprotectants (SAM-e, Milk thistle

(silymarin), Vit E Denamarin®)

What drugs can you give to treat acute hepatitis?

Lactulose, oral tylosin/metronidazole/neomycin

What is VERY VERY VERY important for supportive care?

glucose

What is the most common hepatobiliary disease in cats?

Feline Hepatic Lipidosis

What characterizes Feline Hepatic Lipidosis?

haracterized by the accumulation of excessive

triglycerides (TGs) in more than 80% of the hepatocytes

85% of cats have a primary disease that triggers ____ that causes HL

anorexia

What is the pathophysiology behind Feline Hepatic Lipidosis?

Cat stops eating → negative energy balance → fat mobilization → lipidosis→ liver failure

Cats are strict carnivores and are unable to synthesize ___

EFA's

Cats have limited ability to adapt their protein metabolic pathways for conserving ____ and they rapidly develop essential ___ ___ deficiency and protein malnutrition after a period of anorexia

nitrogen, amino acid

There is an imbalance between the influx of NEFAs derived from peripheral fat stores, de novo synthesis of FAs, the rate of hepatic FA oxidation for energy, and the dispersal of hepatic TGs via excretion of very low-density lipoproteins (VLDLs).- this is red on the slide

okay girl ik it <3

T/F Cushing's and Fatty Liver is hard to differentiate

True

What are the history and clinical findings of feline hepatic lipodosis?

• Historical obesity

• Anorexia and weight loss

• Icterus, dehydration, vomiting, nausea and ptyalism,

constipation or diarrhea, and a poor hair coat

• mentation of cats with FHL can be severely altered if

hypokalemia and HE are present.

• Ventroflexion of the neck, severe muscle weakness

What deficiency causes ventroflexion of the neck?

hypokalemia

How do you diagnose Feline Hepatic lipodosis?

• Presumptive

• Underlying disease processes can confuse the picture

How do you get a definitive diagnosis of feline hepatic lipidosis?

liver FNA (greater than 80% of the hepatocytes )

What will you see on serum biochemistry with feline hepatic lipodosis?

• ↑ Bilirubin, ↑ ALP and ALT

• BUN may be decreased (chronic anorexia)

• Hypokalemia, hypomagnesemia, and hypophosphatemia

How do you treat feline hepatic lipodosis broadly?

1. Fluids and electrolytes

2. Nutrition

3. Antinausea/antemetics

4. Vitamin K1

What type of fluids should be avoided when trying to treat feline hepatic lipidosis?

glucose rich fluids

What type of fluids should be used fro FHL?

Crystalloid

Electrolytes should be corrected (before/ after) nutrition is started because ____ release can cause a further (increase/ decrease) in serum/plasma potassium and phosphate concentrations

before, insulin, decrease

What is the cornerstone of treatment for FHL?

nutrition