L17: Clinical Approach To Elevated LIV Enzymes (Gallagher)

Question 1

Hepatic enzymes

Answer 1

-Alkaline phosphataseALKP
-Gamma-glutamyl transferase (GGT)
-Alanine aminotransaminase (ALT)
-Aspartate aminotransaminase (AST)
(LDH in large animal)

do NOT tell anything about liver function!!

Question 2

Where are liver enzymes located in the hepatocytes?

Answer 2

ALP: on apical hepatocyte membranes, and bile canaliculi membranes

AST: majority in mitochondria, some in cytosol (requires more cell damage to be released)

GGT: same places as ALP, except more in canaliculi

Question 3

ALKP properties

Answer 3

• an inducible enzyme released in response to cholestatic dz, drugs (anti-convulsants, steroids)
• has multiple isoenzymes esp. In liver and bone
• will be increased in young growing puppies, and older dogs with nodular hyperplasia
• dogs have a steroid-inducible isoenzyme that is not present in the cat
• cat ALP has shorter half-life than in dogs, so if ALP is elevated in cats, it is always important!

Question 4

GGT properties

Answer 4

• membrane-associated
• inducible enzyme from cholestatic dz, drugs
• Dogs have higher SPECIFICITY: If GGT is increased in dogs, there is a lower likelihood of it being a false + than in cats
• Cats have higher SENSITIVITY: if increased, less likely it is a false neg.
• If ALP is normal but GGT is elevated in a cat, still suspicious of liver dz

Question 5

ALT properties

Answer 5

• Cytosolic
• Liver specific enzyme
• necrosis/inflammation (due to drug toxicity, trauma, etc.) –> greatest increases
• small amount can come from the muscle

Question 6

AST properties

Answer 6

• in cystosol/mitochondria
• requires more damage before released
• less specific to liver (also comes from muscle, RBCs)
• can be falsely elevated in iatrogenic hemolysis or IMHA
• If AST > ALT, muscle damage or hepatobiliary disease likely –> irreversible damage

Question 7

If AST > ALT**

Answer 7

Muscle damage is likely

-look for CK for marker of muscle damage: if CK is normal but AST > ALT, suggests irreversible damage to the hepatocytes

Question 8

Breed-related liver problems: Dobies, Bedlingtons, Labs, Yorkies, Chis, Schnauzer, Scotties

Answer 8

Dobies: chronic hepatitis
Bedlingtons: Cu storage hepatopathy
Labs: Cu-associated hepatitis
Yorkies, Chis, schnauzers: PSS
Scotties: benign hyperalkaline phosphatemia

Question 9

Common drugs or toxins causing liver damage

Answer 9

• steroids, NSAIDs, anti-convulsants

- sago palms, mushrooms, aflatoxins

Question 10

Abnormalities on PE with liver damage

Answer 10

-Icterus
-Hepatomegaly
-Ascites
-Skin lesions
(Hepatocutaneous syndrome: ulcerative, hyperkeratotic skin lesions, commonly on pad)

Question 11

Where do cats usually become icteric first?

Answer 11

Soft palate

Question 12

MILD increase in ALP, ALT, AST is what X above upper reference range?

Answer 12

2-5X

Question 13

MODERATE increases in ALP, ALT, AST is what X above upper reference range?

Answer 13

5-10X

Question 14

MARKED increases in ALP, ALT, AST is what X above upper reference range?

Answer 14

> 10X

Question 15

Indirect markers of liver function

Answer 15

Chem: BUN, Albumin, Cholesterol, Glucose, Bilirubin
CBC: microcytosis
UA: ammonium urate crystals

Question 16

Why can liver damage –> microcytosis?

Answer 16

Liver responsible for making transferrin which shuttles Fe. If transferrin low, have problems making normal RBCs
-can also see with PSS

Question 17

Which breeds predisposed to urate crystals?

Answer 17

Dalmatians and bulldogs (so not necessarily assoc. with liver dysfx)

Question 18

If ALP is highest liver enzyme, main differentials should include:

Answer 18

Things that cause cholestatic dz or drugs that induce isoenzymes

Question 19

If ALT is highest liver enzyme, should suspect what kind of dz?

Answer 19

Dz that causes hepatocellular damage (ie. NSAIDs)

Question 20

Increased ALP with normal or near normal GGT indicative of:***

Answer 20

Hepatic lipidosis

Question 21

Anything that causes cholestatic dz will also cause a degree of hepatocellular damage and vice versa

Answer 21

Rarely isolated increases in enzymes

Question 22

Liver function tests

Answer 22

Bile acids/urine bile acids

Ammonia (fasting and tolerance testing)

Question 23

Circulation of bile acids

Answer 23

Synthesized in liver –> GB –> duodenum during a meal –> ileum

90% reabsorbed back into portal circulation, 10% in feces

95% of bile acids in portal circulation goes back to liver, 5% goes to systemic circulation

Question 24

Bile acids test

Answer 24

Fast, then measure bile acids in systemic circulation before and after giving a small fatty meal

• can be influenced by biliary obstruction, GI dz in ileum –> false negatives
• false positives due to whether animal truly fasted or not, if GB contracted or not
• degree of increase not assoc. with specific liver dz, unless >100, which is assoc. with PSS
• hemolysis and lipemia can also affect results
• don’t do in PSS or icteric patients

Question 25

Urine bile acids test

Answer 25

- indication: animals with PSS that can't do normal bile acids test w/o becoming very hypoglycemic - doesn't require fasting - measures bile acids in urine

Question 26

Ammonia tolerance test

Answer 26

Measures ammonia level before and after injecting ammonium chloride in the colon. - if high, liver not functioning properly - rarely used

Question 27

Fasting ammonia level

Answer 27

- useful in icteric patients that can't do bile acids test | - can evaluate liver fx and look for evidence of encephalopathy

Question 28

Why don't do bile acids test in icteric patient?

Answer 28

Is redundant because bile acids follow same pathway so if bilirubin is increased, bile acids are also increased most likely

Question 29

Why can fasting ammonia lvl be normal in patient with encephalopathic signs?

Answer 29

If fasted long enough, blood will eventually get to liver and ammonia will get down to normal; we aren't actively challenging the liver

Question 30

Coagulation tests

Answer 30

- PT/PTT - Protein C *important tests to do if planning to biopsy the liver

Question 31

If PT/PTT is prolonged, what should you give before performing liver biopsy in dogs?

Answer 31

fresh frozen plasma

Question 32

If cats have prolonged PT/PTT and hepatic lipidosis, what should be supplemented before liver biopsy?

Answer 32

Vitamin K

Question 33

Usefulness of measuring Protein C

Answer 33

To differentiate between PSS and portal vein hypoplasia - if low, more likely PSS - if normal, more likely portal vein hypoplasia (aka microvascular dysplasia)

Question 34

Imaging for detecting liver dz: pros and cons of abd. Rads, US, CT

Answer 34

Abd rads: can evaluate liver size and look for problems outside liver, but not very helpful otherwise Abd US: can see nodules but won't know what they are w/o aspirates or biopsy. If used with contrast, may be able to differentiate b/w malignant and benign nodule Abd CT: can diagnose PSS and location of shunt

Question 35

Types of tissue sampling for liver

Answer 35

- FNA, cytology of specific masses, diffuse neoplasia, or poor inflammatory conditions - Biopsy

Question 36

Pros and cons of liver cytology

Answer 36

- only about 40% correlation between cytology and histo results - poor for inflammatory conditions, cholestasis, fibrosis - good ID of masses, diffuse neoplasia, vacuolar hepatopathy +/- hepatic lipidosis

Question 37

Liver anatomy

Answer 37

- hepatocytes are functional unit and metabolically active - stellate cells part of immune system in liver - bile duct flows opposite blood flow - portal and hepatic a. At periphery, central vein in center - central v. Carries blood out liver and back to vena cava

Question 38

3 types of liver biopsy and pro/con of each

Answer 38

1) US guided: relatively noninvasive, can't get large samples 2) Laparoscopy: can get larger samples and look at other organs and the liver, more invasive 3) Laparotomy: good for when you suspect mass will need to be removed, most invasive